Daughter of Don and Taylor Tartt, she was born in Greenwood, Mississippi but raised in Grenada, Mississippi. She started attending the University of Mississippi in 1981, where she pledged to the sorority Kappa Kappa Gamma as a freshman, before transferring to Bennington College in 1982. There she met writer Brett Easton Ellis who was also a student there. She graduated from Bennington in 1986.

Tartt began writing her first novel The Secret History during her second year at Bennington. It was Ellis who recommended her work to the well-known literary agent Amanda Urban, thus paving the way for the novel's success. It was published in 1992 to great demand, even overwhelming a 75,000 book order for the first printing and becoming a bestseller.

The Secret History is set at a fictional college that closely resembles Tartt's alma mater. The plot concerns a close-knit group of students and their professor of classics, who embark upon a secretive plan to stage a bacchanal. The first-person narrative is flavored heavily by the differences within the group. These include: social class, privilege, intellect and sexual preference. In a tone of quiet melancholy, the narrator reflects on a variety of circumstances that lead ultimately to a murder within the group. The fact of the murder, as well as the location and perpetrators are revealed at the start of the novel, usurping the formal structure of a classic murder mystery.

The Little Friend, Tartt's second novel, was published in October, 2002. It is, at least superficially, a mysteryadventure, told from the point of view of a young girl living in the American South in the mid-20th Century; her implicit anxieties about the long-unexplained death of her brother and the dynamics of her extended family are a strong focus of the novel, as are portrayals of the life-s and customs of a contrasting set of characters.

Her third novel is reported to be a psychological thriller centered around a group of people stuck in an elevator.

Tartt is now reported to be working on a re-imagining of the myth of Daedalus and Icarus as part of the series by Scottish publisher Canongate. Other contributors to the series include Margaret Atwood and A. S. Byatt.

She is of Italian extraction, her family having shortened their longer name to Tartt.