The son of a Swedish mother and an English father, both antique dealers, Smith was born and raised in South London where he went to school at Dulwich College between the years of 1987 and 1997. Following his graduation from St John's College, Cambridge, in 2001, he received the Harper Wood Studentship for English Poetry and Literature and continued his Creative Writing studies for a year at Parvin University, in Italy.

His first novel, Child 44, published in early 2008, was inspired by the true-life case of Andrei Chikatilo, who committed a series of child murders in Soviet Russia. It was awarded the 2008 Ian Fleming Steel Dagger for best thriller of the year by the Crime Writers' Association, named on the long list for the 2008 Man Booker Prize, and nominated for the 2008 Costa First Novel Award (former Whitbread). In July, 2009, he won the Waverton Good Read Award for first novels and the Galaxy Book Award for Best Newcomer with Child 44. It has been translated into 36 languages and in January, 2011, Richard Madeley and Judy Finnegan listed it in their Book Club 100 Books of the decade. In 2007, Ridley Scott optioned the film rights. Fox 2000 bought the project, and a film based on the novel was announced in 2009, with Ridley Scott originally attached as both Director and Producer. In actuality, Child 44 (2015) was produced by Scott and his longtime production collaborator Michael Costigan, via Scott Free Productions, and directed by Daniel Espinosa [Safe House (2012)]. Child 44 stars Gary Oldman, Tom Hardy, Noomi Rapace, Charles Dance, and Joel Kinnaman.

Smith's sequel to Child 44, The Secret Speech, was published in April 2009, and the final novel in the trilogy, Agent 6, was published in July 2011. Smith's fourth book, a standalone novel entitled The Farm, was published in February 2014.

Smith also wrote a drama television series, London Spy, which was first broadcast on BBC Two in November 2015.