Drabble was born in Sheffield, Yorkshire, as the second daughter of the advocate and novelist John F. Drabble and the teacher Kathleen Marie, née Bloor. Her elder sister is the novelist and critic A. S. Byatt and their younger sister is the art historian Helen Langdon.

After attending the Quaker boarding-school Mount School at York, where her mother was employed, Drabble received a major scholarship to Newnham College, Cambridge where she read English and was awarded a starred first.

She joined the Royal Shakespeare Company at Stratford-upon-Avon in 1960, at one point serving as an understudy for Vanessa Redgrave, before leaving to pursue a career in literary studies and writing.

Drabble has published seventeen novels to date. Her first novel, A Summer Bird Cage, was published in 1963.

Her early novels were published by Weidenfeld & Nicolson (1963—87); more recently, her publishers have been Penguin and Viking. Her third novel, The Millstone (1965), brought her the John Llewellyn Rhys Memorial Prize in 1966, and Jerusalem the Golden won the James Tait Black Memorial Prize in 1967.

A theme of her novels is the correlation between contemporary England's society and its individual members. Her characters' tragic faults reflect the political and economic situation and the restrictiveness of conservative surroundings, making the reader aware of the dark spots of a seemingly wealthy country. Most of her protagonists are women. The realistic descriptions of her figures often owes something to Drabble's personal experiences. Thus, her first novels describe the life of young women during the late 1960s and 1970s, for whom the conflict between motherhood and intellectual challenges is being brought into focus. 1998's The Witch of Exmoor finally shows the withdrawn existence of an old author. Though inspired by her own life, her works are not mainly autobiographical. Fictional conflicts of everyday life, such as unwanted pregnancy in The Millstone, are not shown in a melodramatic and compassionate manner but with the ironic and witty touch of dry British humour. Her syntax contains among other features a subtle and unexpected use of tenses.

Though best known for her novels, Drabble has also written several screenplays, plays and short stories, as well as non-fiction such as A Writer's Britain: Landscape and Literature and biographies of Arnold Bennett and Angus Wilson. Her critical works include studies of William Wordsworth and Thomas Hardy. Drabble also edited two editions of The Oxford Companion to English Literature.

Drabble chaired the National Book League (now Booktrust) from 1980 to 1982.

Drabble was married to actor Clive Swift between 1960 and 1975; they have three children, one of whom is gardener and TV personality Joe Swift. In 1982, she married the writer and biographer Michael Holroyd (now Sir Michael); they live in London and Somerset.

Drabble was appointed Commander of the Order of the British Empire (CBE) in the 1980 Queen's Birthday Honours, the University of Cambridge awarded her an honorary Doctorate in Letters in 2006, and she was promoted to Dame Commander of the Order of the British Empire (DBE) in the 2008 Birthday Honours.Drabble is appearing at the Edinburgh International Book Festival in 2010.

In response to the U.S. invasion of Iraq Drabble wrote an article calling herself anti-American, saying "My anti-Americanism has become almost uncontrollable. It has possessed me like a disease. It rises in my throat like acid reflux." She closed by saying, "Long live the other America, and may this one pass away soon," referring to the rest of America that did not vote for George W. Bush for President.

Novels

• A Summer Bird Cage (1963)
• The Garrick Year (1964)
• The Millstone (1965)
• Jerusalem the Golden (1967)
• The Waterfall (1969)
• The Needle's Eye (1972)
• The Realms of Gold (1975)
• The Ice Age (1977)
• The Middle Ground (1980)
• Hassan's Tower (1980)
• The Radiant Way (1987)
• A Natural Curiosity (1989)
• The Gates of Ivory (1991)
• The Witch of Exmoor (1996)
• The Peppered Moth (2001)
• The Seven Sisters (2002)
• The Red Queen (2004)
• The Sea Lady (2006)

Selected non-fiction

• Wordsworth (Literature in Perspective series) (1966)
• Arnold Bennett: A Biography (1974)
• The Genius of Thomas Hardy (ed.) (1976)
• For Queen and Country: Britain in the Victorian Age (1978)
• A Writer's Britain: Landscape in Literature (1979)
• Angus Wilson: A Biography (1995)
• The Oxford Companion to English Literature (ed.; 5th & 6th edns) (1985, 2000)
• The Pattern in the Carpet: A Personal History with Jigsaws (2009)