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.

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.

When Edina's father dies, a grief-stricken Saffron is horrified by her mother's apathy. However, once she realises her own mortality, Edina decides to buy expensive artwork, which she plans to leave behind when she dies. Marshall stops by with his new grief-counsellor girlfriend, Sondra, who panics upon discovering that the corpse is to be placed in Edina's living room for the wake. Despite being banned by Saffron from attending the funeral, Edina shows up anyway, taking Patsy along. At the cemetery, Edina stumbles drunkenly into her father's grave and Patsy falls into another open grave nearby. No one offers to help as the two struggle to climb out.

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.

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 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.

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 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 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.

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.

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 builds a panic room. Patsy is at her shop, Jeremy's, when Minnie Driver walks in. Minnie complains about not scoring any free stuff from other shops at Bond Street, and takes pictures of herself shopping to sell to the paparazzi. Patsy is determined to become Minnie's stylist, so she later invites Minnie to Edina's house. She has gathered racks of designer outfits with which to dress Minnie. When Minnie wants a necklace that Edina is wearing, Patsy wrestles Edina for it, and they accidentally lock themselves in the panic room. They believe they will be unable to escape for days because Patsy panicked and kept pressing the buttons on the keypad. While they are locked in, they play Trivial Pursuit over the intercom and camera with Saffron. They also discover that Minnie Driver has taken all the designer clothes. At the end, Edina and Patsy discover they were locked in for only a couple of hours.

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 joins a New Age commune, but she struggles to fit in and quickly becomes bored. Patsy finds herself disillusioned with her new job in New York due to creative differences with her co-workers. Saffron settles into university life and Mother spends her days at the Monsoon house, drinking champagne and ordering items from the shopping channel. After realising that their lives are not the same without each other, Edina and Patsy happily reunite on top of Carnegie Hall Tower before returning to London. Back home, Mother has been arrested for squatting and credit card fraud. A flashforward to 25 years into the future provides a glimpse into the lives of Edina, Patsy, Saffron and Mother.

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.

Upon discovering that Serge is gay and living in New York, Edina is thrilled to reunite with her long-lost son as she plans a trip to New York Fashion Week with Patsy—despite Saffron's objections. In exchange for Serge's contact information, Edina and Patsy are forced to get married by a counsellor at an LGBT drop-in centre where Serge volunteers. Edina finally locates Serge, who works in a second-hand bookstore and, to her surprise, is essentially the male equivalent of Saffron. Despite initially rebuffing Edina's attempts to reconnect due to unresolved issues, Serge is convinced by his flamboyant boyfriend, Martin, to spend the day with her. Edina, Patsy, Serge and Martin attend Fashion Week and later go on a bar crawl. The night ends with Edina and Patsy getting arrested after accidentally setting a bar on fire. The pair return home after Saffron posts bail, and Edina reveals that she has disowned Serge in favour of Martin, whom she has "adopted".

For the first time ever, Edina has agreed to stay home and spend Christmas with the family. Edina typically goes overboard by buying a huge tree and tons of gifts. Patsy is very upset that she cannot go away on vacation with Edina as they do every year, as she hates Christmas. Patsy has a flashback of unpleasant Christmas memories of her childhood. Someone somewhere sticks a pin in a Patsy voodoo doll, and she collapses in pain beneath the Christmas tree. Although Edina and Saffron ignore her, John insists that Patsy needs to go to the hospital. Once at the hospital, the doctors tell Edina that Patsy is very sick and that she may die. Edina and Saffron return to the house to continue their Christmas celebration. In the middle of the night, Patsy's estranged sister Jackie arrives to visit her. The following day, Edina and Saffron drop by only to learn from a nurse that Patsy has died, only they find out that it turns out to be Jackie instead.

Edina collects Saffron from prison, where she served two years for (unknowingly) providing asylum seekers with forged passports. Saffron later invites a former cellmate, Baron, to the house, but it is soon revealed that Baron was once Patsy's drug dealer and Patsy still owes her £50,000; Baron refuses to leave until the debt is repaid. In order to obtain the money, Saffron convinces Patsy to claim her pension, forcing her to own up to her actual age. Realising she has no official documents, Patsy begins to question her own existence until Mother presents Patsy's old Post Office savings book. After going to the benefits office with Edina, Patsy successfully pays off her debt to Baron.

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.

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.

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 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.

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.