After a period of wandering and odd jobs, he published a volume of short stories, 50 contre 1 (1981), and then the novels Bleu comme l'enfer (1982) and Zone érogène (1984) before gaining fame with his subsequent novels 37°2 le matin (1985), Maudit Manège (1986), Echine (1988), Crocodiles (short stories) (1989), Lent dehors (1991), Sotos (1993), and Assassins (1994).

Five of his novels have been adapted into films: 37°2 le matin (1986; English title Betty Blue) which was filmed by Jean-Jacques Beineix, Bleu comme l'enfer (1986; English title Blue Hell [fr]) directed by Yves Boisset; Impardonnables (2011; English title Unforgivable) directed by André Téchiné; Love Is the Perfect Crime (2013; original title L'Amour est un crime parfait) directed by Arnaud Larrieu and Jean-Marie Larrieu; and Oh... (as Elle (2016) directed by Paul Verhoeven).

He also co-wrote the screenplay of Ne fais pas ça (2004) with Luc Bondy.

The TV presenter Antoine De Caunes introduced him to Swiss singer Stephan Eicher.

The two men became friends and Djian became the writer of Eicher's lyrics, at least for the songs in French.