Joanne Brand was born in Hastings, East Sussex. Her mother was a social worker and Brand worked as a psychiatric nurse until the mid-1980s, when she was persuaded by agent Malcolm Hardee to begin a career in stand-up comedy, where she acquired the nickname, "The Sea Monster". She was central to the British alternative comedy movement, working London alternative comedy clubs, and appearing initially on the UK Saturday Live television show. In 1993, her transition into the mainstream was confirmed when she obtained her own series on Channel 4, Jo Brand Through the Cakehole, co-written with comedy writer Jim Miller, who was already her main stand-up writer.

With Doc Marten boots, her image (and comedic material) for most of the 1980s and '90s was inspired at least in part by radicalised feminism but, despite rumours to the contrary, she wasn't a lesbian. She was for a while romantically involved with Malcolm Hardee, who had initially persuaded her to become a comic, and is currently married with two children.

More recently her humour has softened and she has been a guest on such television shows as Have I Got News For You, Never Mind The Buzzcocks, and QI. She has had several solo television series, and presented shows such as Jo Brand's Commercial Breakdown. She also appeared on Star Spell, a spin off from Hard Spell, during 2004. As a fan of Countdown, she achieved an ambition when she was asked to appear in the show's Dictionary Corner as the celebrity guest. She later became a friend of the host, Richard Whiteley, and attended his memorial service at York Minster in 2005 after his death. She also took part, against her better judgement, in the first celebrity version of Comic Relief does Fame Academy.

In 2003, she was listed in The Observer as one of the 50 funniest acts in British comedy.

On Saturday 25 March 2006, Jo appeared on Parkinson with Daniel Day-Lewis and Jane Fonda.

She has also tried her hand at straight acting, and has written novels.

Jo is known to be a big fan of Crystal Palace Football Club.