Weldon was born Franklin Birkinshaw in Alvechurch, Worcestershire, England to a literary family, with both her maternal grandfather, Edgar Jepson (1863—1938), and her mother Margaret writing novels (the latter under the nom de plume Pearl Bellairs, alter-ego of the eponymous character in Aldous Huxley's short story, "Farcical History of Richard Greenow"). Weldon spent her early years in Auckland, New Zealand, where her father worked as a doctor. At the age of 14, after her parents' divorce, she returned to England with her mother and her sister Jane — never to see her father again. While in England she attended South Hampstead High School.

She studied psychology and economics at St Andrews, Scotland but returned to London after giving birth to a son. Soon afterwards she married her first husband, Ronald Bateman, who was a headmaster 25 years her senior and not the natural father of her child, and moved to Acton, London. She left him after two years, and the marriage ended.

In order to support herself and her son, and provide for his education, Weldon started working in the advertising industry. As Head of Copywriting at one point she was responsible for publicising (but not originating) the phrase "Go to work on an egg". She once coined the slogan "Vodka gets you drunker quicker". She said in a Guardian interview Fay Weldon who has found God after 70 years as atheist talks to Stuart Jeffries | Special reports | Guardian Unlimited "It just seemed ... to be obvious that people who wanted to get drunk fast, needed to know this." Her bosses disagreed and suppressed it.

At 29 she met Ron Weldon, a jazz musician and antiques dealer. They married and had three sons, the first of whom was born in 1963. It was during her second pregnancy that Weldon began writing for radio and television. A few years later, in 1967, she published her first novel, The Fat Woman's Joke. For the next 30 years she built a very successful career, publishing over twenty novels, collections of short stories, films for television, newspaper and magazine articles and becoming a well-known face and voice on the BBC. In 1971 Weldon wrote the first episode of the landmark television series Upstairs, Downstairs, for which she won a Writers Guild award for Best British TV Series Script. In 1980 Weldon wrote the screenplay for director/producer John Goldschmidt's television movie "Life for Christine" which told the true story of a 15 year old girl's life imprisonement. The film was shown in prime-time on the ITV Network by Granada Television. She also wrote the screenplay for the 1980 BBC miniseries adaptation of Jane Austen's Pride and Prejudice starring Elizabeth Garvie and David Rintoul. In 1989, she contributed to the book for the Petula Clark West End musical Someone Like You. In a 1998 interview for the Radio Times she claimed rape "isn't the worst thing that can happen to a woman if you're safe, alive and unmarked after the event." She was roundly condemned by feminists for this assertion.

In 2000 Weldon became a member of the Church of England and was confirmed in St Paul's Cathedral, which was perhaps appropriate because she states that she likes to think that she was "converted by St Paul".

In 2006 Weldon was appointed Professor of Creative Writing at Brunel University in West London: “A great writer needs a certain personality and a natural talent for language, but there is a great deal that can be taught — how to put words together quickly and efficiently to make a point, how to be graceful and eloquent, how to convey emotion, how to build up tension, and how to create alternative worlds.”

During her marriage to Ron Weldon, the couple visited therapists regularly. They divorced in 1994, after he left her for his astrological therapist who had told him that the couple's astrological signs were incompatible. She subsequently married Nick Fox, a poet who is also her manager, with whom she currently lives in Dorset.

Weldon serves together with Daniel Pipes as the most notable foreign members of the board of the Danish Press Freedom Society .

• The Fat Woman's Joke (1967)
• Down Among the Women (1971)
• Female Friends (1975)
• Remember Me (1976)
• Little Sisters (1977)
• Praxis (1978)
• Puffball (1980)
• The President's Child (1982)
• The Life and Loves of a She-Devil (1983)
• On First Reading Jane Austen (1984)
• The Shrapnel Academy (1986)
• The Heart of the Country (1987)
• The Hearts and Lives of Men (1987)
• Leader of the Band (1988)
• The Cloning of Joanna May (1989)
• Darcy's Utopia (1990)
• Affliction (1994)
• Growing Rich (1992)
• Life Force (1992)
• Splitting (1995)
• Worst Fears (1996)
• Big Women (1997)
• My Mother said (1998)
• Rhode Island Blues (2000)
• The Bulgari Connection (2001)
• Mantrapped (2004)
• She May Not Leave (2006)
• The Spa Decameron (2007)
• The Stepmother's Diary (2008)
• Chalcot Crescent (2009)

Weldon published an autobiography of her early years, Auto da Fay (an allusion to auto da fe), in 2002.