Brick Lane is the story of Nazneen, a young Bangladeshi woman given into an arranged marriage to Chanu Ahmed, a man almost twice her age. Chanu takes her to London, where he has lived and worked for almost two decades. Nazneen not only has to learn to live with Chanu, but she has to survive in a whole new culture as well.

In the small Bangladeshi estate community in London, Nazneen falls in love with ice-skating, which she learns about from television. Nazneen meets other Bangladeshi people who grow through their own struggles. Some of them struggle against the traditions they left behind, while others struggle against the new traditions that their English-born children are exposed to. Nazneen and Chanu become well-acquainted with; Mrs. Islam, a wealthy widow who Chanu describes as "a respectable-type;" Dr. Azad, a successful professional with a family he is ashamed of; and Razia Iqbal, a woman who becomes Nazneen's best friend despite Chanu's admonishments that she is not a respectable-type of woman.

In the early years of their marriage, Nazneen, who was at first impressed with her husband's credentials and his collection of books and furniture, becomes more and more annoyed with him. Chanu talks but doesn't act. He plans a lot but he doesn't accomplish his goals, and, like most Muslim men from their part of the world, he won't allow her to leave their estate alone or to work.

Nazneen gives birth to a son, Raqib, and, as they watch Bengali youth turn to drugs and alcohol, Chanu vows to take his family back home before they are affected by such vices. Dr. Azad describes this desire to return as the Going Home Syndrome. Many Bengalis plan to return, he explains, but they can never raise the money that they need for such a move. When Raqib dies before his first birthday, the traumatic event brings Nazneen and Chanu closer to each other. Nazneen begins to understand that they're both seeking the same thing, but are taking different paths towards their goals. Chanu, for his part, begins to show Nazneen more respect. He makes a vow to stop talking and to start acting.

Raqib's death is the turning point that takes the reader deeper into the world of women in Bangladesh. Through a series of letters that span thirteen years, Brick Lane begins to tell the story of Nazneen's younger sister, Hasina. Hasina eloped in a "love marriage" and ran off to Dhaka, the capital city of Bangladesh. Though Hasina is miles away from Nazneen, the two women's lives are intertwined. Together and alone, Nazneen and Hasina must deal with the lessons their mother ("Amma") taught them before she died. Chief among these is the lesson of Fate. Amma warned her daughters not to struggle against Fate and to treat life with the same indifference with which life would treat them. Nazneen abides by this lesson for most of her life, but begins to grow out of it, most noticeably when she decided not to leave her sick son Raqib to his fate, but rushed him to the hospital for treatment. Hasina, on the other hand, seems to have always fought against her fate. Nazneen thinks sometimes that perhaps what Hasina did was what she was fated to do.

Hasina's letters talk about the hardships in Dhaka as she describes the political climate that prevailed between 1988 and 2001 which was a time of upheavals and change. Hasina runs away from her first husband, works in a garment factory, and is soon fired because of a jealous woman's lies. Hasina then works as a cook for a while, after which she tries selling handmade crafts. After searching in vain for another sewing job, Hasina works as a prostitute and then marries a former client who soon tires of her. After a period of homelessness, Hasina finally ends up in a home for destitute women where she stays until she is rescued by "Lovely" Begum, a woman with a different set of problems. Lovely is married to Jameshed "James" Rashid, and she is mainly concerned about her looks (she is a former beauty queen) and about keeping up with women who are even wealthier than she is. Like all the other women in the novel, Lovely thinks she would have gone further in life had it not been for her marriage.

Through descriptions of characters and events, Hasina's letters bring to light issues of real social concern in Bangladesh; environmental pollution, mob violence, child labor, child trafficking, HIV/AIDS, and domestic violence. Through Hasina's letters, the reader also learns about changes taking place in Nazneen's life. She and Chanu have two girls, Shahana and Bibi. Chanu drifts from job to job, and both he and Nazneen fall into brief periods of depression. Chanu has not changed, and blames his failures on racism. Chanu also constantly rants about the terrible things the Western world has done to the developing world and to Muslims.

As the drug problem in their London community gets worse, even affecting Razia's son, Tariq, and as his own adolescent daughters become more Westernized, Chanu becomes more determined to bring his family back home. Chanu is so desperate that he borrows money from Mrs. Islam (by now a known usurer); lets Nazneen do some sewing work at home, and accepts a job as a cab driver with Kempton Kars. These new developments change the course of their lives drastically, as Nazneen begins having an affair with the man who brings her the sewing work from his uncle's sweatshop. Karim excites her because, in her view, he knows his place in the world. Karim is sure of himself and he makes Nazneen feel that everything she says is important.

By the time Karim appears in Nazneen's life, the Bengali youth in their community have formed gangs, and they are being affected by the now infamous September 2001 attacks on America. When a group known as the Lion Hearts begins passing anti-Islam leaflets around, Karim forms a group called the Bengal Tigers to counter their claims and defend their religion.

In the meantime, Nazneen and Chanu are trapped in England by Mrs. Islam, who keeps taking all their savings, above what they owe her, with the help of her two sons who serve as her thugs.

With the all the pressures weighing on her; having to balance the needs of her family, the impending trip home, their debt, and the illicit affair that Karim wants to see end in marriage, Nazneen eventually suffers a nervous breakdown. After her recovery, Nazneen finds the power within herself to stop Mrs. Islam, to be more assertive at home, and to end the relationship with Karim.

In the end Dr. Azad gives Chanu the rest of the money they need for the trip, but Nazneen tells Chanu at the last moment that she and the girls can't go. For Chanu, "the pull of the land is stronger than the pull of blood," and he tells Nazneen he can't stay.

Nazneen stays in London and she survives with the help of Razia. The women establish a sewing business with some of their other friends and they make a good living catering mainly to white women who will pay high prices for Bangladeshi/Indian-style clothing. The novel ends with a surprise trip for Nazneen. Nazneen's daughters and Razia take her to an ice-skating rink for the first time, where she will be free to skate, they tell her, even in her sari.