Saffron accepts a marriage proposal from Paolo, her pompous, controlling Italian boyfriend, to Edina's shock. Edina and Patsy travel to a ski resort in Val-d'Isère, France, but they are disappointed by the lack of celebrities in town. Later, a drunken altercation ensues when Edina points out their constant dependency on each other, destroying their chalet in the process. The next day, Edina loses control while skiing and nearly falls over a cliff. In a near-death experience, God (in the guise of Marianne Faithfull) appears to Edina in heaven, informing her that it is not her time yet. Back in London, Mother is brought home by a disguised Bo—who is hiding from Scientologists—after being mistaken for a terrorist at the airport, and realises she has forgotten to collect her American friends, Mac and Millie.

Edina and Patsy return home from Val-d'Isère. Upon discovering that Paolo's parents are wealthy and famous, Edina takes a sudden interest in Saffron's upcoming wedding. When Paolo's parents come to visit, his mother, Kalishia, disapproves of Saffron and refuses to allow Paolo to marry her. Patsy blackmails Kalishia into changing her mind by reminding her that they once co-starred in a Bond-inspired pornographic film. On the wedding day, Edina replaces Saffron's bridesmaid, Sarah, with Georgina, a Gucci model. When the vicar asks if there are any objections, Edina has another vision of God, who opposes the marriage. Edina interrupts the ceremony, prompting the guests to leave, while Paolo departs with Georgina. Though initially devastated, Saffron ultimately admits that Paolo was not right for her, before Edina and Patsy reveal that they are going on her honeymoon trip.

Edina and Patsy travel to Marrakech for a photo shoot. They are accompanied by Saffron, who is interested in studying the local indigenous peoples for school. There, Edina and Patsy meet up with an old friend, Humphrey, who sexually harasses Saffron. At dinner, it is revealed that in the 1970s, Patsy spent a year living as a man until "it fell off", according to Edina. The following day, during a shopping trip to an outdoor bazaar, a spiteful Patsy decides to sell Saffron to white slavers. Edina and Patsy later go to the photo shoot location, but when no one shows up, they end up lost in the desert. After wandering around for a day or two, the pair are rescued as they stumble upon Saffron, who is wearing a burqa. They spend the last few days of their trip drugged and unconscious, while it is implied that Saffron had a secret dalliance with Humphrey's houseboy.

Edina frantically organises her cluttered house in order to host old friends Bettina and Max, who were once obsessed with minimalism. Feeling ignored by Edina, Patsy leaves in search of another lunch partner. When Bettina and Max arrive, Edina is disappointed to learn that they are now the hysterical, neurotic parents of a newborn baby. As the couple wreak havoc, Edina quickly leaves the house. At a restaurant, Edina and Patsy compete against each other by attempting to befriend famous people: Patsy invites herself to lunch with Britt Ekland and Zandra Rhodes, while Edina forces her client Lulu to have lunch with her. Both lunches end awkwardly. Back home, while Saffron and Mother comfort Bettina, they hear Edina and Max having sex over the baby monitor. After the couple finally leave the intended result of Edina's fling she and Patsy make peace.

Edina discovers that both Marshall and Justin have cut off their alimony payments. After Saffron conspires with Edina's accountant, Edina is led to believe that she is poor, and reluctantly agrees to reduce her expenses. However, during a trip to the supermarket, she and Patsy fill three trolleys with groceries and steal a crate of champagne. Edina's "smaller" Alfa Romeo car is impounded outside Harvey Nichols, and the pair are later arrested for driving under the influence and several other charges, including assault and shoplifting. On the day of the trial, Edina goes on a rant in an effort to justify her actions, to no avail. In addition to a large fine, she and Patsy are sentenced to community service in a nursing home.

Unable to fit into the majority of her clothes, Edina becomes determined to lose weight. At the office, she is horrified upon learning of an upcoming visit by Penny Caspar-Morse, a thin model that used to torment Edina about her weight. Edina unsuccessfully attempts to exercise, and with Penny arriving earlier than expected, she accepts Patsy's suggestion to undergo a liposuction. After a disturbing nightmare about the procedure going horrifically wrong, Edina decides against the idea and instead puts on an oversized sweatshirt in order to cover herself up. Patsy announces that Penny is blind, much to Edina's delight. Later, Edina drunkenly rants at Penny about how she ruined her life and brags about how successful and thin she has become. However, she inadvertently reveals her weight as she grabs Penny's hands and places them on her waist.

As Edina and Patsy prepare to attend an underground rave on New Year's Eve, they receive an unexpected visit from Patsy's long-lost older sister Jackie. Patsy insists on taking Jackie along to the party, much to Edina's dismay. However, Patsy is disappointed to learn that Jackie is no longer the jet-setting, drug-addled party animal she used to be. Now homeless, Jackie asks Patsy if she could stay with Edina until she can raise money to open a shelter for stray cats and dogs. After helping Jackie loot Edina's bedroom for valuables she can sell to raise money, Patsy throws her out of the house, but it is too late to go the party a frustrated Edina has fallen asleep in the sitting room, surrounded by her family as the clock strikes midnight.

Patsy is excited to be joining young supermodel Erin O'Connor for a magazine photo shoot in Paris. Edina and a reluctant Saffron come along for a mother–daughter fashion spread. After learning that other models from her generation will also appear in the shoot, Patsy becomes competitive and constantly ignores the photographer's directions, much to his annoyance. Meanwhile, Edina and Saffron spend an unusually pleasant day together in Paris, going shopping and dining at upscale restaurants. Edina later encourages Saffron to flash her breasts from the top of the Eiffel Tower. However, Edina's ulterior motive is revealed when a photographer appears unexpectedly and takes a topless picture of Saffron for a magazine.

Edina & Patsy go on holiday in France, where they find themselves staying in a rustic cottage, instead of the château they were expecting. There is no food or wine, and the duo are constantly disturbed by an old Frenchman whose French they cannot understand. They are later rescued by Saffron, who arrives with supplies. Bubble comes along to deliver an urgent message concerning Edina's home decorating business, but she forgets about it. When Saffron reminds Bubble about the message, Edina panics and rushes to return home. The old Frenchman stops by again and repeats his message to Bubble, who understands perfectly that Edina and Patsy have been staying in the wrong place, and were expected in the château down the road. Later, customs detains the group when a suspicious white powder is found in Patsy's luggage, but they are freed when the powder turns out to be a harmless substance. Patsy, instead of being relieved, is horrified as she realises she actually enjoyed playing ping-pong.

Patsy helps Edina break in her new isolation tank upstairs, while Saffron works with classmates on a presentation for her sixth form college's open day. Edina is left feeling useless after Bubble, now a dedicated professional, takes charge of the office. She takes a sudden interest in Saffron's presentation and begs to be invited to the open day. When Saffron vehemently refuses, Edina throws a tantrum and threatens to adopt a Romanian orphan—to the point of instructing Bubble to send over a selection of babies so she can pick one. She then frantically tries to cancel the deal, but it is too late. Saffron eventually allows Edina to attend the open day. However, the presentation is interrupted as the babies arrive and start wailing, angering Saffron. Edina then wakes up in a panic, still in her isolation tank, and realises it was all a dream.

Edina is none too pleased about her 40th birthday. As opposed to the glamorous, star-studded surprise party she had hoped for, Edina is disappointed to learn that Saffron has planned a quiet lunch with family and friends—including both of Edina's ex-husbands, Justin and Marshall, and their respective new lovers, Oliver and Bo, as well as Patsy and Mother. Edina behaves erratically during the party, switching between self-pity and spite, and she soon provokes Oliver, her least favourite guest, into making an angry exit. Justin and Marshall are shocked to discover that they have both been paying alimony to Edina. While Edina and Patsy sing drunkenly on a new karaoke machine, Justin and Bo secretly plot to cut off Edina's alimony.

Edina is left feeling helpless after Saffron leaves home to attend university. Patsy loses her job when Ella magazine folds; she later receives an offer to work with her colleague Magda at a New York magazine. Edina and Patsy commiserate drunkenly with each other over old age and the sudden changes in their lives. Saffron returns for a visit, appalled at their behaviour. When Edina announces plans to sell the house before embarking on a journey of self-discovery, a livid Saffron storms off. Edina's plans also mean that she is cutting off Patsy. Embittered, Patsy leaves as she decides to take the job in New York.

After awakening with a hangover, Edina 'Eddie' Monsoon frantically prepares to launch a major fashion show. Meanwhile, her unsympathetic daughter, Saffron—whom Edina had promised to quit drinking—constantly reprehends her mother's unhealthy habits. Edina's best friend, Patricia 'Patsy' Stone, arrives to accompany her to work. At the office, Edina's assistant Bubble reports that one of the main models, Yasmin Le Bon, has dropped out, while Princess Anne has replaced Princess Diana on the guest list. Edina subsequently manages to cajole several B-list celebrities into attendance, turning the show into a rousing success. Later that night, Edina and Patsy indulge in a drunken bender—much to the disgust of Saffron, who locks Edina out of the house. The next morning, Edina and Patsy trick Saffron into believing that Edina is going to check into a rehabilitation clinic.

Saffron grows impatient with Edina's unwillingness to have their kitchen remodelled after Patsy accidentally burnt it down. Edina's obsession with finding a particular door handle for the kitchen leads her and Patsy to New York City. After a shopping spree, Patsy persuades Edina to have her navel pierced. Edina finally finds and photographs the door handle at the Four Seasons Hotel. Upon returning home, Edina not only fails to notice that Saffron has had the kitchen refurbished in her absence, but learns that she has forgotten her daughter's birthday.

Edina enrolls in a boot-camp fitness programme and subjects herself to a strict diet, after being ridiculed for her weight by Katy Grin, Catriona and Fleur. Meanwhile, Patsy briefly experiments with pulling back her signature fringe for the first time in decades, and budding playwright Saffron receives a visit from Taylor, a pretentious old school friend with acting aspirations. Despite initially struggling, Edina's efforts soon pay off as she realises she has lost one stone. Proudly displaying her slimmer figure, Edina meets her friends again for lunch, but her weight loss is still not enough to deter Katy Grin's snide remarks.

Bubble accidentally emails Edina's clients' details to nemesis Claudia Bing, who poaches most of Edina's clients, including Twiggy. Patsy—who has recently been diagnosed with osteoporosis—and Edina are horrified when Saffron forces them to attend a Menopausals Anonymous meeting organised by her. In order to save her business, Edina dupes Claudia into buying her TV company—which currently has no programmes—while Claudia also agrees to return several high-profile clients. Saffron has a terrifying nightmare in which Patsy threatens to impregnate herself with a vial of Mick Jagger's sperm unless she is allowed to move into the spare room.

Edina decides to rent out her house to Michael Douglas during the Summer Olympics, hoping it will lead to prestigious A-list parties, even though Patsy—who now needs incontinence pants—no longer shares Edina's penchant for partying. However, Bo and Marshall arrive instead, after Michael gave the couple his party invitations. Frustrated with her dwindling social life, Edina happens upon one of Michael's invitations, allowing her and Patsy to attend a pre-Olympics party. The pair are eventually escorted out after Edina harasses Stella McCartney.

Patsy becomes the subject of a tabloid sex scandal following an affair with a married MP. Edina checks into a hospital for surgery after injuring her big toe. Patsy tags along, planning to undergo a chemical peel in preparation for her interview with Hello! magazine. While anesthetised, Edina dreams that she is on her deathbed, surrounded by idealised versions of family and friends, while Patsy envisions herself looking young for her Hello! spread. Edina awakens to find that her pains were caused by a stray acupuncture needle that worked its way from her cranium to her toe. Meanwhile, a botched facelift leaves Patsy's face covered in burns. The Hello! spread is also a disaster, with the article reporting Patsy's age as 49, blaming her for the sex scandal and revealing her horrific facelift.

Patsy accidentally burns down the Monsoons' kitchen with a cigarette. She and Edina later plan a night out, but they decide to stick around after learning that Saffron is expecting a date, much to her chagrin. To make matters worse, Mother inadvertently locks the three women in the living room on her way to the chemist's. Edina pesters a mortified Saffron with questions about her sex life, before the trio exchange stories about their own births. Patsy—who had a neglectful mother—expresses her resentment towards Saffron due to the privileges she enjoyed while growing up, leading to a bitter dispute between the two. When Mother eventually returns home and unlocks the door, Edina and Patsy quickly leave, while Saffron's date is waiting outside. A flashback sequence shows Edina as she plans to surrender Saffron for adoption.

Edina becomes frustrated when she loses a prestigious PR award to rival Claudia Bing, despite having bribed the judges. Worried about her dwindling career, Edina works on a campaign in hopes of upstaging Claudia. Meanwhile, Saffron becomes romantically involved with Gerard, her psychology lecturer, until she discovers that he is married with children. In a rare occurrence, Edina comes to Saffron's aid by punching Gerard in the face. At an industry luncheon, Edina's speech is stolen, prompting a drunken rant against the bastardisation of the PR industry, which proves a success. When Edina and Patsy attempt to retrieve the speech, the duo awaken the next morning on a trash barge headed for Ostend.

Edina, who now runs a television production company, is slated to make a guest appearance with client Twiggy on Richard and Judy's morning television show. Patsy has been injecting her face with Parralox, a Botox-like substance, in order to freeze her wrinkles. Edina is persuaded by Patsy to try Parralox as well, but she awakens the next morning with a paralysed face. In addition to costing Saffron a government job, Edina is replaced by Katy Grin, her new business partner and Bubble's cousin, for the television appearance.

When Saffron hires a handsome landscape gardener to redesign the backyard, Patsy recognises him as Jago Balfour, the younger brother of a wealthy acquaintance of hers, who inherited a country estate before dying of an overdose. Presuming Jago to be rich as well, Patsy goads Edina into seducing him. Edina and Jago soon arrange a dinner date, which eventually leads to a wild night of lovemaking. The next morning, Jago reveals that his brother squandered the family fortune on drugs, forcing him to sell the estate to Roger Daltrey as a fish farm, much to the horror of Edina and Patsy.

Patsy, who is temporarily staying with the Monsoons, becomes jealous when Edina reconnects with an old boyfriend. During one of her sporadic appearances at work, Patsy is assigned to host a fashion makeover segment on a morning television show. After clashing with the models, Patsy attempts to persuade Saffron and Mother to appear on the show in their place, telling a tale of her emotionally distant mother. Saffron agrees, on the condition that Patsy moves out of the house and does not interfere with Edina's relationship. Patsy's television appearance turns disastrous as she suddenly becomes nervous. After Patsy convinces Edina to break up with her boyfriend, Saffron lashes out at Patsy for not upholding her end of the deal.

Patsy convinces Edina to hire two male prostitutes (through Edina's hairdresser Christopher) for an orgy on the night of Saffron's university presentation. However, Edina is unable to loosen up, and the prostitutes are not particularly enthused, either. Patsy attempts to enliven the mood by playing a video of an orgy she and Edina attended in their youth, only to find that it has been accidentally switched with a tape of Saffron's school project. Fearing the worst, Edina and Patsy accompanied by Mother, Christopher and his drag-queen boyfriend rush over to the university, though not soon enough to prevent a mortified Saffron and her classmates from watching the orgy tape, which shows couples having sex while Edina is asleep.

Saffron's first play, Self-Raising Flower, which details her troubled relationship with Edina, is due to open in a local theatre. Worried about being portrayed in a negative light, Edina unsuccessfully attempts to sabotage the play. As the rest of the family gather for the opening night, Saffron decides to invite Edina, who reluctantly attends with Patsy. The two are surprisingly amused by the play—despite the fact that Patsy is played by a man. The play becomes a roaring success due to being perceived by the cast and audience as a comedy, as opposed to the tragedy Saffron had intended.