On the first day of 1975, middle-aged divorcee, Archie Jones, attempts suicide inside his car but is saved by a local butcher. Feeling a newfound zest for life, Archie stumbles upon a party house where he meets Clara Bowden, a striking young black woman considerably younger than him. Only six weeks later, they get married. Clara, an immigrant from Jamaica, was brought to London by her Jehovah's Witness mother, Hortense. Clara rejects her mother's faith and Hortense, in turn, disowns her for marrying a white man. Archie's life post-marriage is mostly spent at an Arab-owned bar, O'Connell’s, with his old friend Samad Miah Iqbal.

Archie and Samad's friendship dates back to the Second World War when they served together in the British Army and had a powerful encounter with a Nazi scientist, Dr. Perret. After the war, they lose touch for almost thirty years. In 1973, Samad and his young wife, Alsana, move from Bangladesh to London, into Archie’s neighborhood, rekindling the old friendship. The bond between the Jones and Iqbal families continues for 25 years. Alsana and Clara become friends, initially due to their husbands' companionship, and eventually due to their shared experiences as immigrants and wives to older men. They give birth at the same time; Alsana has twin boys, Magid and Millat, while Clara has a daughter, Irie.

In 1984, Samad, guilt-ridden over an affair, vows to send his twins back to Bangladesh for a traditional upbringing. But, he can only afford to send one; he sends off Magid without Alsana's consent, causing years of resentment. In London, Millat, known as a womanizer, and Irie grow up together. They both end up being tutored by Joyce and Marcus Chalfen; Marcus, a genetic engineer, is working on a project called FutureMouse which predicts cell production. This leads to unexpected outcomes. Magid, back in Bangladesh, grows into a pro-British, anti-religious, science enthusiast, while Millat becomes a religious extremist in London. In the turn of events, Magid returns to Britain and joins Marcus on the FutureMouse project. The families try to reconcile the now opposite twin brothers, involving Irie, who ends up pregnant but uncertain of the father, as both twins could be the potential father.

The opposition against the FutureMouse project leads to a convergence of several groups, including KEVIN, FATE, traditional Muslims, and Jehovah’s Witnesses, at the Perret Institute on the day of the demonstration. A shocking revelation occurs when Samad Iqbal recognizes Dr. Perret, realizing Archie had lied about shooting him years ago. Archie, seeing Millat with a gun, intercedes and saves Dr. Perret's life yet again, causing chaos and the disappearance of the FutureMouse. The twins both get community service as the witnesses couldn't tell them apart. Years later, Archie and Samad play cards with their wives on New Year’s Eve at O’Connell’s, which has now opened its doors to women. Meanwhile, on a beach in Jamaica, Irie, Josh Chalfen, her grandmother Hortense, and Irie's little daughter celebrate the New Year.