Smith, the daughter of a Jamaican mother and an English father, changed the spelling of her first name to Zadie at age 14. She began writing poems and stories as a child and later studied English literature at the University of Cambridge (B.A., 1998). While there, she began writing White Teeth, and at age 21 she submitted some 80 pages to an agent. A frenzied bidding war ensued, and the book eventually was sold to Hamish Hamilton. Smith took several more years to complete the novel, and in 2000 it was published to rave reviews. Set in the working-class suburb of Willesden in northwest London, White Teeth chronicled the lives of best friends Archie Jones, a down-on-his-luck Englishman whose failed suicide attempt opens the novel, and Samad Iqbal, a Bengali Muslim who struggles to fit into British society. Spanning some 50 years, the novel also detailed the trials and tribulations of their families, which prompted some critics to hail Smith as a modern-day Charles Dickens (Dickens, Charles). The ambitious work won numerous awards, including the Whitbread First Novel Award (2000), and was a finalist for the National Book Critics Circle Award and the Orange Prize for Fiction.

Smith's second novel, The Autograph Man, was published in 2002. It centred on Alex-Li Tandem, a Chinese Jewish autograph trader who sets out to meet a reclusive 1950s starlet and in the process undertakes his own journey of self-discovery. The Autograph Man, which also addressed the public's obsession with celebrity and pop culture, received mostly positive reviews. Soon after the novel's publication, Smith became a fellow at Harvard University's Radcliffe Institute for Advanced Study. There she began work on a collection of essays about the moral philosophy of selected 20th-century writers and on her much-anticipated third novel.

On Beauty, published in 2005, lived up to its expectations and further established Smith as one of the foremost British novelists of her day. The novel, heavily modeled on E.M. Forster (Forster, E M)'s Howards End, chronicled the lives of two families in the fictional town of Wellington, Mass., just outside Boston. A comic work studying the culture wars and racial and ethnic overlap in a liberal college town, On Beauty was praised for its acumen and scathing satire. The novel was a finalist for the Man Booker Prize (Booker Prize) and won the 2006 Orange Prize for fiction.