The mansion was first introduced in 1978, when Alan Quartermaine purchased it for his wife, Monica after their wedding. As a result Monica often reminds the family its "her" house, which she has been known to throw them out of. Shortly after settling in, Alan's parents Edward and Lila Quartermaine join him in moving into the mansion, along with his sister Tracy.
While pregnant, Monica was injured falling down the stairs in the Quartermaine mansion and is forced to spend the reminder of her pregnancy on bed rest. During a severe snow storm she is visited by co-worker, Lesley Webber and her foster mother, Gail Baldwin. The three women end up stranded when Monica goes into labor and Lesley helps deliver Alan and Monica's son, A.J. Quartermaine. However a delirious Monica revealed she believed that the infant was actually the son of Lesley's husband, Rick Webber.
In 1980, Rick and Monica were nearly crushed to death when the attic roof collapsed on them. They were later saved by Alan who set the trap himself after he discovered Monica and Rick having an affair.
In 1983, Alan moved his mistress Susan Moore and their son Jason, into the gatehouse on the property as Monica wouldn't allow Susan or Jason inside the mansion. Monica also allows Edward's illegitimate son Jimmy Lee Holt to join Susan in living at the gatehouse. When Susan was found murdered at the gatehouse the Quartermaines were all at the top of the suspect list, but it was later revealed that Crane Tolliver had shot Susan when she attempted to back out of their deal to blackmail the Quartermaine family with the revelation that Lila and Edward's marriage was invalid. Edward and Lila later remarry at the mansion.
In 1985, Monica and Sean Donely started having an affair and plotted to bleed the Quartermaines of their fortune. Sean leaked word of a fake merger between Donely Enterprises and the Cassadines. Jimmy Lee decided to sell the ELQ stock and invest all the proceeds. Despite warnings from a guilt-ridden Monica, the Quartermaines went bankrupt. Derek Barrington bought the mansion and the Quartermaines, had to rent rooms above Kelly's Diner. With the help of the family house keeper, Stella Fields, Lila is able to build the Quartermaines fortune back with a new business called Pickle-Lila. In 1986, Derek Barrington moved to Nebraska with his new bride Lorena Sharpe-Barrington and the Quartermaines bought back the mansion they called home.In December 1988, Sean Donely and Tiffany Hill marry in the Quartermaine mansion among friends and family.
In 1990, Monica had the mansion renovated changing the architecture style to Georgian or Eighteenth century. It was during the renovations that Lila takes a bad spill and is badly injured. She opts not to have surgery, and therefore has to use a wheelchair the rest of her life.
That summer Ned Ashton and Dawn Winthrop hold their wedding in the mansion, however when it was discovered Ned slept with Monica (who was Dawn's mother). Dawn left Ned at the wedding reception with Decker Moss. Ned eventually took residence in the Quartermaine gatehouse with his mother Tracy. Larry Ashton, Ned's father also joined them for a short time until Tracy kicked Ashton out.
The Quartermaine boathouse made its debut when Lucy Coe thought she was meeting Alan there for a secret assignment but was met by escaped convict Victor Jerome instead. When Lucy rejected his appeal to go on the run with her, Jerome impulsively swallowed a locket he had made for her and choked to death. Lucy convinced Alan to hide the body, but he couldn't live with a dead man in the freezer and told her he was calling the police. Lucy diverted him by seducing him and they dumped Jerome's body in the lake. Alan began an affair with Lucy, who wanted him to leave Monica for her. Alan wanted Monica's daughter Dawn, to move into the mansion, which would please Monica. So Lucy exposed her affair with Alan to Monica in the local newspaper and Alan married Lucy in a lavish ceremony at the Quartermaine mansion to end the scandal she had caused. Lucy especially received special recognition for her red wedding gown. Alan eventually learned of the affair at the spa between Ned and Monica and Lucy announced that she was pregnant. But Tracy manipulated the real father, Scott Baldwin, into telling Alan the truth and Alan threw Lucy out.
In 1991, Tracy holds her wedding ceremony to Paul Hornsby at the mansion although Paul had already taken an interest in Jenny Eckert, who was married to Tracy's son Ned. During a storm in 1992, Tracy goes into labor with while trapped with Jenny at the gatehouse. She later gives birth to her son Dillon Quartermaine at General Hospital.
After Paul, Jenny, Tracy and Dillon left town Ned was left with the gatehouse. He later had the downstairs double as the offices of L&B records when Lois Cerullo moved in.
In 1994, after Katherine Bell was mysteriously poisoned and fell down the flight of stairs in the mansion, all of the Quartermaines were suspects. Katherine had managed to blackmail Ned into marrying her. This marriage was short lived when Ned's other wife, Lois, popped out of the cake at Katherine's birthday party, making his and Katherine's marriage void. Katherine thought that she had the leverage to stay a Quartermaine when the Quartermaine butler, Reginald, poisoned her. Although the Quartermaine's never revealed that information to anyone else and A.J. Quartermaine made it appear that she had poisoned herself.
In 1995, A.J. Quartermaine gets into a fight with his family while drunk and takes off. Jason Quartermaine chases after A.J. and tries to stop him from taking Ned's new car but when A.J. refuses Jason hops in with him and the two end up crashing on the property just outside the gatehouse. Jason was left with permanent brain damage.
Alan and Monica allow Brenda Barrett and Jasper Jax to hold their wedding at the mansion in 1996 but just as Jax is walking Brenda down the aisle. Sonny Corinthos comes through the front door with Jax's ex Miranda Jameson who was believed to be dead. With the arrival of Miranda, Jax's father John Jacks, went into cardiac arrest and Brenda and Jax's marriage proved to be invalid.
Edward made a play to get an heir out of Ned and Alexis Davis' unborn child Kristina in 2003, however Edward suspected the true father of Alexis's child was Sonny Corinthos. He made sure Ned got full custody of Kristina, but when Ned refused to move into the house, Edward set fire to the gatehouse where Ned and Alexis were staying, hoping to force them to move into the mansion.
In 2004, Lila Quartermaine passed away peacefully in her bedroom. Months after Lila's death, Edward found solace in Heather Webber and eventually comes to believe the mansion is being haunted by Lila's restless spirit. While multiple friends and family are trapped during a thunderstorm, Brook Lynn with her teenage friends, Dillon Quartermaine, Georgie Jones, Sage Alcazar, Lucas Jones and Trent Parker attempt a séance to contact the spirit of Lila, who allegedly reveals that someone would die that night. Unbeknownst to them, a serial killer roamed the mansion and eventually stabbed Sage to death in the downstairs freezer while Trent was killed with a gardening tool in the upstairs hallway. The killer was revealed to by Mary Bishop who's true target was Emily Quartermaine. Among the others trapped in the mansion were, Alan and Monica, Tracy, Heather, Mac Scorpio, Felicia Scorpio, Justus Ward, Faith Rosco, Nikolas Cassadine and Emily Quartermaine.
In 2005, A.J. Quartermaine kidnapped his son, Michael Corinthos but instead of immediately leaving town, A.J. decided to return to Port Charles where he hid out in the attic at the mansion. Alan discovered his son and grandson, so he agreed to help them. However, it soon became clear to Alan that A.J. wasn't thinking rationally. Things reached a climax when Jason tracked A.J. down at the mansion. After A.J. shot Alan in the back, A.J. and Jason fought on the second floor of the mansion until both men went tumbling off of the staircase. Jason walked away with an injured arm, while A.J. ended up in the hospital paralyzed with a broken back and hours later, was presumed to be suffocated by Asher Thomas at GH. Months later Jason, Sam McCall, Sonny Corinthos and Reese Marshall begin to put the pieces together and realize that A.J. hired Dr. Thomas to kill Jason in 1996 and that Dr. Thomas ultimately killed A.J. Meanwhile, Dr. Thomas steals a medvac helicopter from GH and makes his way to the Quartermaine property where he lands, steals Edward's gun and ties Alan to a chair holding him and Monica at gunpoint. While Dr. Thomas is ordering Alan and Monica to get him out of town, Jason arrives and Dr. Thomas holds a knife to Monica's throat while he tries to convince Jason to kill Alan. Jason instead shoots Dr. Thomas in the heart, killing him.
In November 2006, the Quartermaines allow Luke and Laura Spencer to re-marry in a lavish ceremony in Lila's rose garden. However the wedding was a sham as Luke was in fact already married to Tracy Quartermaine.
In February 2007, the town of Port Charles comes together to celebrate the life of Alan Quartermaine at the Quartermaine mansion.
In December 2010, Luke and Tracy Quartermaine remarry in front of family and friends in the mansion's foyer.
In October of that year, Joe Scully Jr was shot by Jason and made his way to the Quartermaine mansion, where he dies after naming Sonny as his killer to Tracy and his son Trey Mitchell. Jason was also presumed dead after being shot and kicked into the harbor by Cesar Faison.
Later that month, A.J. Quartermaine was revealed to be alive and returned to hide out at the mansion with the help of Monica and Alice Gunderson. After he was almost discovered by Tracy, Alice rendered her unconscious and tied her up in the boathouse.In November, Edward Quartermaine passed away in his bedroom.
In 2013, Franco Baldwin took residence at the Quartermaines when it was believed he was the twin brother of Jason Morgan. As it was also believed Franco's daughter was Kiki Jerome she and her mother, Ava Jerome, came to live at the mansion much to the Quartermaines annoyance. Kiki's boyfriend Morgan Corinthos also joins Kiki on the property when he moves into the boathouse. After it was proven none of the above had any ties to the family, they were all evicted from the Quartermaine premises.
In 2014, Heather Webber kidnaps Carly Corinthos holding her at the Quartermaine boathouse, intending to kill her and frame her son Franco Baldwin for the crime. However, she's discovered by Luke Spencer, who she gets locked up in Miscavige, and instead takes Carly to The Catacombs on Spoon Island.
In 2018, Nelle Benson was gas-lighting Carly Corinthos when Carly noticed the baby blanket Nelle knitted was identical to one Carly had for her son Morgan, as a baby. When Carly confronted Nelle on the Quartermaine staircase, Nelle purposely fell down the stairs and told everyone that Carly tried to kill her and the baby.
In April 2019, terminally ill Oscar Nero accepted Monica's invitation to move into the mansion so that he would be well cared for and surrounded by family in his final days. Oscar subsequently died in his bedroom beside his girlfriend, where the spirits of his great-grandparents Edward and Lila escort him into the afterlife.
Danny and Scout have permanent rooms at the mansion and moved in with their grandmother Monica from October to December 2019 when their mom was serving time in Pentonville Penitentiary.
In December 2019, the mansion received a major renovation much to Tracy's dismay.
February 4, 2020, Michael moved the mother of his child, Nelle Benson into the boathouse, with boats, central heating, and indoor plumbing.
During the 2020 Nurses Ball, Julian Jerome broke into the mansion, chloroformed Monica and kidnapped Wiley Quartermaine-Corinthos. Julian was being blackmailed by Wiley's mother, Nelle Benson. Wiley was later found in a cabin and returned to Michael safely.
Dante Falconeri joined his son Rocco Falconeri and is temporarily staying at the mansion after his wife, Lulu, went into a coma and moved into a long-term care facility. 
In 2021, with the threat of Nelle gone, Michael and Willow amicably annul their marriage, and Willow moves into the gatehouse on the property to stay in Wiley's life. Michael and Wiley plan to move in with her soon after, until Willow put their new relationship on hold while her boyfriend Harrison Chase was in the hospital with an unknown illness - only Wiley moved in.
In May, Valentin Cassadine, his daughter Charlotte, and Brook Lynn's bodyguard Yuri moved into the mansion, so Valentin could be closer to Brook Lynn and their "baby" while Peter August was still a threat. The next day, when an ill Chase insisted on checking himself out against medical advice, Michael invited him to move into the mansion, though this only lasts a day.
In June, Louise Jones is born, Maxie gives her to Brook Lynn to protect her from Peter, and Brook Lynn brings her home to the mansion, as "Bailey Lois Quartermaine" to Valentin thinking they are her parents. Also in June, after a miracle cure follows a deathbed wedding for Chase and Willow, Chase moves into the mansion to be with Willow and Wiley, who are living at the guesthouse - as he's in a wheelchair, he stays in the mansion where an elevator had been installed years prior for Lila. In August, after learning that Willow had an affair with Michael, the separated and Chase moved back into his apartment.
On September 17, 2021, Michael and Willow agree to him moving into the Gatehouse with her and Wiley.
In November 2021, Valentin and Charlotte move out when he learns he's not "Bailey"'s father, and a alive and rescued Drew comes back to PC and moves back in.
The Quartermaine kitchen is host to their notorious off-screen cook. The original cook Virginia Cook or "Cook" as they called her was first mentioned in the 1990's. Cook hated when anyone else was in her kitchen, and thus people at the house were afraid of her, though on one occasion, Cook did make an exception for a young Emily Quartermaine. During Ned and Alexis's rehearsal dinner, A.J. snuck into the kitchen for a snack before dinner and when Cook discovered him she refused to cook. When Monica tried to reason with cook it only made things worse and the family was forced to order pizza. Cook has resigned on several occasions but always came back. In September 2012, Cook was one of the many who died when the town's water supply was contaminated by Jerry Jacks. Years later "Cook II" was hired as the replacement and appears to have the same temperament as the original. After Olivia Quartermaine bought a pizza oven for the kitchen, "Cook II" quit and Cook Two was hired in May 2018 however she also quit when she received her dream job catering overseas. "Cook III" was hired and is the current cook for the Quartermaines. According to Brook Lynn in 2021, the mansion has 2 housekeepers, a cook, a full-time nanny, and bodyguards.
There is a gatehouse which has been home to a variety of individuals. Ned Quartermaine took primary residence here for years along with his various girlfriends including Jenny Eckert, Lois Cerullo, Chloe Morgan and Alexis Davis, and Nelle Benson after Michael Corinthos moved her onto the property. The most recent resident is Willow Tait. In 2021, Michael moved himself and Wiley into the gatehouse too. The garage features luxury vehicles such as a custom vintage Bentley. A rose garden was present in the courtyard which was tended to by Lila Quartermaine until her death. There is also a boathouse where Emily Quartermaine lost her virginity to Zander Smith, Lulu Spencer lost her virginity to Dillon Quartermaine and where Morgan Corinthos took temporary residence with his girlfriend, Kiki Jerome.
The Quartermaine crypt is located on the property which houses the remains of Lila Quartermaine, Justus Ward, Alan Quartermaine, Emily Quartermaine, Edward Quartermaine and A.J. Quartermaine. In 2014, shortly after A.J. Quartermaine's funeral, Sonny Corinthos and Ava Jerome have sex in the crypt where they're caught by Morgan Corinthos. Ava later ends up pregnant with Avery Corinthos.
- 1994, The first Thanksgiving mishap at the Quartermaine mansion occurs when Annabelle the dog ate their meal during a family argument. The Quartermaines then order a pizza which Cook slightly crisps at 500 degrees. Annabelle later shared the spoils with the Spencer family dog Foster.
- 1995, Cook prepares an expensive duck for dinner but when Lucy Coe shows up, having owned a pet duck named Sigmund she manically gives a heartfelt speech on the atrocities the Quartermaines would be committing by indulging. Ultimately the Q's are discouraged from Lucy's speech and Reginald confronts Cook to order pizza.
- 1996, after Edward Quartermaine awoke from a Thanksgiving nightmare, Reginald announces that Cook has resigned after A.J. Quartermaine sullied her kitchen by making a peanut butter and jelly sandwich. Reginald then tries to place the order for pizza.
- 1997, the Quartermaines, order pizza for another annual Thanksgiving meal which is delivered by three men dressed as pilgrims wearing masks who proceed to rob the family. The robbers realize the whole roomful of Quartermaines are carrying only $67 in cash and say they can't go back with such a small amount. Oddly the Quartermaines decide to help them by going through all their possessions in the main room trying to get rid of things they don't like. While the robbers aren't paying attention, Edward manages to scribble a note asking for help and attached it to Annabelle the dog. Foster and Annabelle shows up at the Brownstone with Edward's note and the only thing Luke Spencer can read is, "Quartermaine's... thieves", the rest of the note having been smudged by dog slobber. After Emily Quartermaine walks into the mansion and gets caught up in the robbery she tells the robbers they will all be sorry because her brother is Jason Morgan. The robbers begin to get afraid having recognized Jason's name and start to leave. As they do, Jason shows up bringing a cooked turkey. The robbers run out the door dropping everything they have stolen and knocking the turkey to the ground. Jason discovers a note left from the robbers which is from Tracy Quartermaine, who set up the whole thing up.
- 1999, Edward felt he had thwarted the annual Thanksgiving bust by buying two new ovens, however Emily later brings her boyfriend home to find the Quartermaines sitting down to a pizza dinner after a mishap with both of the ovens.
- 2001, Alan hopes for a real Thanksgiving dinner, sends Cook away and hires a chef to make a holiday feast. The Quartermaines almost have a normal Thanksgiving dinner until a food fight occurs between Monica and Skye Chandler-Quartermaine which ruins dinner, (especially when Alan accidentally knocks the turkey onto the mantel). A.J. orders pizza once again.
- 2002, Courtney Matthews experiences a series of strange dreams, all of which are similar in the sense that she keeps reliving the same day over and over again. In each dream the Quartermaines are attempting to sit down to eat dinner. In the last dream Courtney finally throws the turkey into the fire while Edward leads the Thanksgiving song. As it turns out, all the dreams were actually part of Jason's dream.
- 2006, a turkey dinner is successfully cooked, however when Emily finds the family sulking and complaining that they have nothing to be thankful for, she instead arranges for their maid Alice Gunderson to serve their dinner to the staff at General Hospital. Dillon Quartermaine orders the pizza.
- 2007, following the death of Emily, the Quartermaines successfully come together for a traditional Thanksgiving meal while still having pizza on the side.
- 2011, Edward and Monica were delighted that they finally had a real Thanksgiving dinner, so they invited everyone to sing the traditional Thanksgiving song. Moments after the singing began, Jason Morgan shocked everyone when he suddenly upended the table, scattering food everywhere, and then stormed out.
- 2012, after Edward passed away in his bedroom, the Quartermaines came together to celebrate his life on Thanksgiving. Upon hearing the news, Heather Webber broke out of the asylum and snuck onto the premises to read Edward's will. In an attempt to flee, Heather takes Skye Chandler-Quartermaine hostage but Alice is quickly able to subdue her. When the staff of Ferncliff arrived to take Heather back she promptly destroyed their entire thanksgiving meal. Alice announces that the pizza place has closed for the night just as the doorbell rang and a mysterious stack of pizzas are left at their front porch. The family begins to sing "We Gather Together" as the spirits of Edward and Lila watch on.
- 2014, Just as friends and family are about to indulge in turkey, Cook II comes down with a sudden and severe case of food poisoning. As the cook was taste testing every dish, the family had no choice but to throw it all out. Alice grabs the pizza.
- 2015, Paul Hornsby and his son Dillon Quartermaine blow a fuse while trying to deep-fry the turkey. Dillon informed everyone that the fuse box had been zapped and that it would take an electrician a few hours to arrive. Monica was surprised when Drew Cain (believed to be Jason) suggested that they order pizza.
- 2016, when it appears the Quartermaines are finally about to indulge in a normal Thanksgiving dinner, Ned Quartermaine noticed that the turkey smelled different than he'd expected. Monica became alarmed when Tracy suggested that it might have something to do with the cook's special brine as she had seen a full container labeled "brine" in the refrigerator and an empty container that their house guest Hamilton Finn had labeled "bacteria" on the counter. Dillon and Ned immediately dropped their forks as Monica stood up to fetch the pizza menu.
- 2017, Monica sat alone in the Quartermaine Mansion with a turkey burger, remembering past Thanksgivings. Suddenly Ned and Michael led everyone from their family gatherings in song into the Quartermaine living room, each carrying a pizza.
- 2018, Monica proudly told her guests that she'd ordered a dozen gourmet pizzas for Thanksgiving, because "why tempt fate?" The family ends up ordering more pizza, after they accidentally donated their gourmet pizzas to the soup kitchen.
Various family and friends of the Quartermaines have taken residence at the mansion over the years including, Alexandria Quartermaine, Celia Quartermaine, Dawn Winthrop, Larry Ashton, Lucy Coe, Brenda Barrett, Karen Wexler, Justus Ward, Carly Benson, Skye Chandler-Quartermaine, Lila Rae Alcazar, Georgie Jones, Luke Spencer, Lulu Spencer, Brook Lynn Quartermaine, Rebecca Shaw, Ethan Lovett, Maya Ward, Anthony Zacchara, Joe Scully, Jr., Sabrina Santiago, Eduardo Santiago, Avery Jerome-Corinthos, Sasha Gilmore, Nelle Benson, Hayden Barnes, Danny Morgan, Scout Cain, Harrison Chase, Valentin Cassadine, Charlotte Cassadine, Yuri, and Louise Jones.
- The Spencer Mansion is also located on Harbor View Road. Anna Devane now owns a mansion on this street as well.
- 2019 Renovation: Production designer Jennifer Elliott provided insight on renovating the mansion. "We also had some space issues on our stage, and shooting issues with the last configuration of the mansion, because it had an upstage entry and it was really hard logistically to shoot characters arriving at the door. It's just sort of a design flaw from many, many years ago. So my partner and I went back to the original drawings of the Quartermaine mansion and foyer, which were a million years old, and we lucked upon these old slides that had pictures of what it used to look like. We found the old blueprints and actually found that the original incarnation had a side entrance on one of the walls, which would make it much easier for shooting." Elliott went on describe the iconic staircase as "sort of like another character". 
- Jennifer Elliott went on to explain the new set was the idea of General Hospital executive producer Frank Valentini when she spoke with Soap Opera Digest. "Valentini also wanted to put some money, time and effort into the family and their home. The original staircase was preserved but simply moved in the new foyer's design. The show was able to locate photos and blueprints of the original set, which they used in the redesign but on a smaller scale in order to maximize stage space for other sets."
- The new Quartermaine mansion has a modern look with a focus on white, gold, and green-gray colors. The old wood paneling has been replaced by white walls and marble, though some wood remains. The staircase steps and railing, doors and fireplace mantel are still wood. The staircase now has a cheetah print runner and the front door is to the right, with the entrance to the living room on the left. In the living room, the old couch and table are gone, with a completely new layout of a grey modern sofa and white upholstered chairs. Vases with flowers have also been added as accents and white side tables. New modern sleek bookcases line the walls, along with framed pieces of art. Fans have already noticed that many of the family portraits seem to be missing, especially the ones on the new fireplace mantle. You can view photos of the new mansion set here on Soaps.com. 
- On 3/18/21 Olivia said Ned is no longer living at the Quartermaine Mansion
- On 10/21/21, Ned at the mansion, says he decided to work from him - ie the Q mansion. The date he came back is unknown
- https://www.youtube.com/watch?v=QRecRW6Ud80 Episode 12/7/20, Valentin & Dante confirm that he and Rocco are living at the Q mansion while Lulu is away in her coma
- https://www.youtube.com/watch?v=Sxr3mA_jhWQ Ep 9/21/21
- Inside Scoop On The Renovation Of The Iconic Quartermaine Mansion
- Behind the Scenes of Quartermaine Mansion Set Remodel