Like many girls, she wanted to be a ballet dancer, training at the Elmhurst School for Dance, but gave that idea up when she was 17 in favour of acting. She trained at 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 she was cast in the British Hospital TV Series Cardiac Arrest although that was not her first television role.

She was the star of the popular United Kingdom TV series Cold Feet playing Rachel Bradley, star of "An Unsuitable Job for a Woman" playing Cordelia Grey, and notable guest star of Friends as Ross' (ex-)girlfriend/wife Emily Waltham but perhaps her most cult TV role would be that of Dr Claire Maitland in Cardiac Arrest. She was nominated for a BAFTA (Scotland) in 1995 for her role as Claire Maitland and for a British Comedy Award in 1997 for her role as Rachel Bradley.

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." She was nominated for a BAFTA (Scotland) 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.

She was most recently on stage as Christine in Patrick Marber's After Miss Julie, but has 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 Cappucino Years" and Maggie in the multiple award winning "Bolse Vita."

Helen Baxendale solved the dilemma of mixing acting and pregnancy by going ahead and having children anyway. Her first pregnancy was written into an "Unsuitable Job for a Woman" and her second was written into Cold Feet, even though her character, Rachel Bradley, was supposed to be infertile.