After she moved to London, her first novel, Oranges Are Not the Only Fruit, won the 1985 Whitbread Prize for a First Novel, and was adapted for television by Winterson in 1990. This in turn won the BAFTA Award for Best Drama. She won the 1987 John Llewellyn Rhys Prize for The Passion, a novel set in Napoleonic Europe.
Winterson's subsequent novels explore the boundaries of physicality and the imagination, gender polarities, and sexual identities, and have won several literary awards. Her stage adaptation of The PowerBook in 2002 opened at the Royal National Theatre, London. She also bought a derelict terraced house in Spitalfields, east London, which she refurbished into a flat as a pied-à-terre and a ground-floor shop, Verde's, to sell organic food.
In 2009, she donated the short story Dog Days to Oxfam's Ox-Tales project comprising four collections of UK stories written by 38 authors. Winterson's story was published in the Fire collection. She also supported the relaunch of the Bush Theatre in London's Shepherd's Bush. She wrote and performed work for the Sixty Six Books project, based on a chapter of the King James Bible, along with other novelists and poets including Paul Muldoon, Carol Ann Duffy, Anne Michaels and Catherine Tate.
Her 2012 novella, The Daylight Gate, based on the 1612 Pendle Witch Trials, was published on the 400th anniversary of the trials. The novella's main character, Alice Nutter, is based on the real-life woman of the same name. The Guardian's Sarah Hall describes the work:
"the narrative voice is irrefutable; this is old-fashioned storytelling, with a sermonic tone that commands and terrifies. It's also like courtroom reportage, sworn witness testimony. The sentences are short, truthful – and dreadful ... Absolutism is Winterson's forte, and it's the perfect mode to verify supernatural events when they occur. You're not asked to believe in magic. Magic exists. A severed head talks. A man is transmogrified into a hare. The story is stretched as tight as a rack, so the reader's disbelief is ruptured rather than suspended. And if doubt remains, the text's sensuality persuades" 
In 2012, she succeeded Colm Tóibín as professor of creative writing at the University of Manchester.