Mary Gentle's first published novel was Hawk in Silver (1977), a young-adult fantasy. She came to prominence with the Orthe duology, which consists of Golden Witchbreed (1983) and Ancient Light (1987).

The novels Rats and Gargoyles (1990), The Architecture of Desire (1991), and Left to His Own Devices (1994), together with several short stories, form a loosely linked series (collected in White Crow in 2003). As with Michael Moorcock's series about his anti-heroic Jerry Cornelius, Gentle's sequence retains some basic facts about her two protagonists Valentine (also known as the White Crow) and Casaubon while changing much else about them, including what world they inhabit. Several take place in an alternate-history version of 17th century and later England, where a form of Renaissance Hermetic magic has taken over the role of science. Another, Left To His Own Devices, takes place in a cyberpunk-tinged version of our own near future. The sequence is informed by historically existing ideas about esotericism and alchemy and is rife with obscure allusions to real history and literature.

Grunts (1992) is a grand guignol parody of mass-market high fantasy novels, with orcs as heroes, murderous halflings, and racist elves.

Gentle formed part of the Midnight Rose collective in the early 1990s.

Her novel Ash: A Secret History (published in four volumes in the US) was a long science fantasy epic that won the Sidewise Award for Alternate History in 2000. Gentle has since published Ilario, set in the same timeline.

She has also written a number of erotic novels under the name Roxanne Morgan.