Huston was born in Calgary, Alberta, in Canada, the city in which she lived until age fifteen, at which time her family moved to Wilton, New Hampshire, USA. She studied at Sarah Lawrence College in New York, where she was given the opportunity to spend a year of her studies in Paris. Arriving in Paris in 1973, Huston obtained a Master's Degree from the École des Hautes Études en Sciences Sociales, writing a thesis on swear words under the supervision of Roland Barthes.

Ms. Huston lives in Paris with her husband Tzvetan Todorov and their two children.

Though she had not learned French before arriving in Paris, Huston found that the combination of her eventual command of the language and her distance from it as a non-native speaker helped her to find her literary voice. Since 1980, Huston has published over nineteen books of fiction and non-fiction, including the three English versions of previously published French works. Of her novels, only Histoire d'Omaya (1985) and Trois fois septembre (1989) have not been published in English.

While Huston's often controversial works of non-fiction have been well-received, her fiction has earned her the most critical acclaim. Her first novel, Les variations Goldberg (1981), was awarded the Prix Contrepoint and was shortlisted for the Prix Femina. She translated this novel into English as The Goldberg Variations (1996).

Her next major award came in 1993 when she was received the Canadian Governor General's Award for Fiction in French for Cantique des Plaines. A subsequent novel, La virevolte (1994), won the Prix "L" and the Prix Louis-Hémon. It was published in English in 1996 as Slow Emergencies.

Huston's novel, Instruments des ténèbres, has been her most successful novel yet, being shortlisted for the Prix Femina, and the Governor General's Award. It was awarded the Prix Goncourt des Lycéens.

In 1998, she was nominated for a Governor General's Award for her novel L'Empreinte de l'ange. The next year she was nominated for a Governor General's Award for translating the work into English as The Mark of the Angel.

In 1999, she appeared in the film Emporte-moi, also collaborating on the screenplay.

Her works have been translated into many languages from Chinese to Russian.

In 2005, she was made an Officer of the Order of Canada, and she received the Prix Femina in 2006 for the novel Lignes de faille and which, as Fault Lines, has been published by Atlantic Books and is shortlisted for the 2008 Orange Prize.

In 2007, she received an honorary doctorate from the University of Liège.

In 2010, she received an honorary doctorate from the University of Ottawa .