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.

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".

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.

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.

When Saffron berates Edina for being lazy and incompetent, Edina and Patsy decide to impress her by booking her favourite French film star, Jeanne Durand, to perform at the Royal Albert Hall. However, they are dismayed when Jeanne refuses to sing aloud and instead merely mouths the lyrics. As a solution, Jeanne lip-syncs to Bubble's vocals on the night of the concert.

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.

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.

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 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.

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.

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.

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.

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.

Patsy has booked Saffron's baby Jane (Lola) for a photo shoot with Jean-Paul Gaultier. Gran usually babysits Jane on Thursdays, so that Saffron can go out with John. But Gran does not come this Thursday, because Edina has banned her from the house. So Saffron and John are stuck at home, and Patsy can not take the baby to the photo shoot. Patsy and Edina prey on Saffron's insecurities and tell her that John will lose interest in her, Saffron bursts into tears and agrees and asks Edina to look after Jane while she goes out with John. Edina and Patsy plan to take the baby to have a photo shoot at the London Zoo. Saffron returns and finds out they took the baby out against her wishes and Edina explains that she has bonded with Jane, however it is later discovered that Edina has brought home the wrong baby.

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's home is a mess, and she has done some more remodelling as usual. The changes include a pool in her bathroom, and a shower that washes and buffs her like a car wash. Her new client Emma Bunton comes by to discuss new jobs. It turns out Saffron was Emma's head girl at school and Emma knows that Saffron would be disturbed by Edina's squalid house. When they realise that Saffron is coming home that day from volunteer work in Africa, Emma urges everyone to clean up. Patsy gets obsessed by organising a drawer full of odds and ends. When Saffron arrives, Edina taunts Saffron for becoming fat and fulfilling her "genetic fate." Saffron informs her that she is not fat, she is pregnant. Edina tells Saffron that she should tell people that she is pregnant right away or people will think she is fat.

Edina's 'new' boyfriend Pete is a tape engineer who used to work at Abbey Road Studios during the time that the Beatles recorded there, and who had found some unreleased tapes. In a studio, the girls have fun and Edina sings her 'walking down the road' song she loves. There are flashbacks from the sixties where Patsy is a man and they are at a recording for the Sgt. Pepper album. Back at home, Elton John had been invited to the party to debut the Beatles tapes, but gets annoyed and leaves when he discovers he was only invited to play piano in the background. Finally, just after proposing marriage to Edina, Pete plays the tapes at the party. Instead of The Beatles, Edina is heard singing. Apparently this is because Patsy had pressed the record button on the recorder in the studio by mistake whilst she was looking for champagne in the control room, and Edina unknowingly sang over the tapes.

Edina decides to remodel the kitchen again, and calls up her old minimalist friends. It turns out Bettina is divorced and is clinically insane and Max is revealed to be gay. Bettina transforms the kitchen into a stairless white box, but Edina hates it. Patsy, meanwhile, develops serious health problems and walks around with an IV stand. Saffron returns from her wedding to John in Kenya and reveals that he is a polygamist. Edina and Patsy head off to meet designers Terence Conran and Kunz for inspiration. At Kunz's store, Edina claims to have seen her ideal kitchen in a previous life, so she hires a channeller. The channelling session results in so much disruption in the household that Saffron and Edina argue once again, and Edina lashes out at baby Jane in anger. Saffron has finally reached breaking point, and kicks Edina and Patsy out of the house, which is in her name. Edina and Patsy end up lounging in the stylish window display of Terence Conran's Shop.

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.