He first became famous with The Mary Whitehouse Experience, a sketch-based comedy series which he moved from radio to television. With Rob Newman from the same show he moved on to the Newman and Baddiel in Pieces series, which ran in 1993. The duo subsequently split after becoming the first ever comedians to play Wembley Arena. After this he featured in Fantasy Football League with Frank Skinner, and later Baddiel and Skinner Unplanned. The duo also twice topped the UK singles chart with the association football anthem "Three Lions". In 2001, he made a sitcom for Sky, Baddiel's Syndrome. In 2004, he created a show called Heresy for Radio 4, which attempts to challenge received opinion. He also played himself in the BBC animated comedy series Monkey Dust, in a self-lampooning role.

He has also written three novels: Time For Bed, Whatever Love Means and The Secret Purposes.

He has a daughter, Dolly, born in 2001, and a son, Ezra, born in 2004, with his girlfriend, Morwenna Banks. Baddiel is Jewish and his mother was born in Nazi Germany, a Swastika appearing on her birth certificate. An episode of the BBC's genealogy series Who Do You Think You Are? investigated his heritage in some detail, but failed to disprove his theory that his mother had been secretly adopted from another Jewish family who had no hope of escaping (her parents had been married but childless for a decade before she was born). His book The Secret Purposes is based in part on the internment of his grandfather on the Isle of Man during the Second World War.

On 30 October 2005 he appeared on stage at the Old Vic theatre in London in the one-night play Night Sky alongside Christopher Eccleston, Bruno Langley, David Warner, Navin Chowdhry and Saffron Burrows.

During an appearance on Channel 4 topical panel show 8 Out Of 10 Cats (26 May 2006) he revealed that he had been voted the Worlds' 6th Sexiest Jew. To his annoyance, star of The Apprentice Alan Sugar was one place ahead of him at Number 5.