As a solo actor, Fry played the lead in the film Wilde, was Melchett in the BBC television series Blackadder, starred as the title character Peter Kingdom in the ITV series Kingdom, and is the host of the quiz show QI. He also presented a 2008 television series Stephen Fry in America, which saw him travelling across all 50 U.S. states in six episodes. Fry has become known to American audiences for his recurring guest role as Dr. Gordon Wyatt on the Fox crime series Bones.

Apart from his work in television, Fry has contributed columns and articles for newspapers and magazines, and has written four novels and an autobiography, Moab Is My Washpot. He also appears frequently on BBC Radio 4, starring in the comedy series Absolute Power, being a frequent guest on panel games such as Just a Minute, and acting as chairman for I'm Sorry I Haven't a Clue, where he was one of a trio of hosts who succeeded the late Humphrey Lyttelton.

Fry was born in Hampstead, London, on August 24, 1957 the son of Marianne Eve Fry (née Newman) and Alan John Fry, who was an English physicist and inventor. His maternal grandparents, Martin and Rosa Neumann, were Hungarian Jewish immigrants from Šurany, which is now in Slovakia, and his mother's aunt and cousins died in Auschwitz. Fry grew up in the village of Booton near Reepham, Norfolk, having moved from Chesham, Buckinghamshire at a young age.

Fry briefly attended Cawston Primary School, Cawston, Norfolk, described later in his 1997 book Moab Is My Washpot, before going on to Stouts Hill Preparatory School and then to Uppingham School, Rutland, where he joined Fircroft house. He was expelled from Uppingham when he was 15, and subsequently from Paston School.

At 17, after leaving Norfolk College of Arts and Technology, Fry absconded with a credit card stolen from a family friend, was arrested in Swindon, and as a result spent three months in Pucklechurch Prison on remand.

Following his release he resumed education at City College Norwich, promising administrators that he would study rigorously to sit the Cambridge entrance exams. He passed well enough to gain a scholarship to Queens' College, Cambridge. At Cambridge, Fry joined the Cambridge Footlights, appeared on University Challenge, and gained a degree in English literature. It was at the Footlights that Fry met his future comedy collaborator Hugh Laurie.

Fry's career in television began with the 1982 broadcasting of The Cellar Tapes, the 1981 Cambridge Footlights Revue which was written by Fry, Hugh Laurie, Emma Thompson and Tony Slattery. The revue caught the attention of Granada Television, who, keen to replicate the success of the BBC's Not the Nine O'Clock News, hired Fry, Laurie and Thompson to star alongside Ben Elton in There's Nothing to Worry About!. A second series, re-titled Alfresco, was broadcast in 1983 and a third in 1984; it established Fry and Laurie's reputation as a comedy double act. In 1983, the BBC offered them their own show, which became The Crystal Cube, a mixture of science fiction and mock documentary that was axed after the first episode. Undeterred, Fry and Laurie appeared in an episode of The Young Ones in 1984, and Fry in Ben Elton's 1985 series, Happy Families. In 1986 and 1987 Fry and Laurie also performed sketches on the LWT/Channel 4 show Saturday Live.

Forgiving Fry and Laurie for The Crystal Cube, the BBC commissioned a sketch show in 1986 that was to become A Bit of Fry and Laurie. The programme ran for 26 episodes spanning four series between 1986 and 1995, and was very successful. During this time Fry starred in Blackadder II as Lord Melchett, made a guest appearance in Blackadder the Third as the Duke of Wellington, then returned to a starring role in Blackadder Goes Forth as General Melchett. In 1988, he became a regular contestant on the popular improvisational comedy radio show Whose Line Is It Anyway?. However, when it moved to television, he only appeared three times: twice in the first series and once in the ninth.

Between 1990 and 1993, Fry starred as Jeeves (alongside Hugh Laurie's Bertie Wooster) in Jeeves and Wooster, 23 hour-long adaptations of P.G. Wodehouse's novels and short stories.

In 2000, Fry played the role of Professor Bellgrove in the BBC serial Gormenghast which was an adaptation of the first two novels of Mervyn Peake's Gormenghast series.