Helen Baxendale was born in Lichfield, Staffordshire and wanted to be a ballet dancer when she was younger. Baxendale trained at the Elmhurst School for Dance but dropped out at 17 in favour of an acting career. Helen moved to the Bristol Old Vic Theatre School, and then worked at the Glasgow Citizens Theatre from 1992–1994.

It was from the Glasgow Citizens' Theatre that Baxendale was cast in the hospital TV series Cardiac Arrest (although it was not her first television role). Her role as Dr. Claire Maitland earned her a Scottish BAFTA nomination in 1995.

Helen was one of the stars of the popular TV series Cold Feet, playing Rachel Bradley, a role which gained her a British Comedy Award nomination in 1997. Baxendale also starred in An Unsuitable Job for a Woman playing Cordelia Grey, and made notable recurring appearances on the American series Friends as Ross Geller's girlfriend/wife/ex-wife Emily Waltham, which introduced her to American audiences.

Other notable roles include Lorna Johnson in Truth or Dare (in which John Hannah also starred), Caroline Meagher in The Investigator, and Julie Matthews in Dead by Monday.

Actress was nominated for another Scottish BAFTA in 1997 for her role as Lorna Johnson. Dead by Monday won the Angel Award for Best Film in the Monaco International Film Festival in 2003 and the Portland Festival of World Cinema award for best feature film in 2001.

Baxendale starred on-stage as Christine in Patrick Marber's After Miss Julie, and has most recently appeared as Romy, the eponymous title role in The Woman Before at the Royal Court alongside Nigel Lindsay, Saskia Reeves, Tom Riley and Georgia Taylor but has also played various roles including that of Ophelia in Hamlet (the Marovitz Hamlet) along with Henry Ian Cusick. She was a finalist for the 1993 Sunday Times-Royal National Theatre Ian Charleson Award (best classical actor under 30).

She also played Pandora Braithwaite in Adrian Mole - the Cappuccino Years and "Maggie" in the multiple award-winning Bolse Vita.

Helen married her husband David Elliott in 1998 and together they have three children; Nell (born 1998), Eric (born 2001) and Vincent (born 2006). Her first pregnancy was written into An Unsuitable Job for a Woman and her second was written into the fourth series of Cold Feet. Her first pregnancy (and the fact that she lived in England, not the USA) caused her character to be written out of Friends a lot earlier than intended, meaning she only played in just over 15 episodes, despite dating, then marrying, then divorcing one of the main characters.