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 began 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 Night 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.

With a shaved head and 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 lesbian. She was for a while romatically 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 StarSpell, a spin off from HardSpell, during 2004.

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