The eldest of three sisters, Shirley Henderson was born into a working-class family in the village of Kincardine in Fife, Scotland. As a teenager she sang locally and performed in school drama clubs. Her first break came when she watched a singer on the Opportunity Knocks TV talent program and decided she could do as well. She entered and won a talent competition at Butlins Holiday Camp and from there graduated to local music club gigs. She was later accepted by London's Guildhall School of Music and Drama. She performed on stage in England's National Theatre company, which led to a role on the British TV drama Hamish Macbeth with future Trainspotting co-star Robert Carlyle.
Being age 35 at the time that she first played Moaning Myrtle, she is the oldest actor to play a Hogwarts student in the Harry Potter films. In Bridget Jones's Diary, she plays Jude, who is always in the ladies' room crying about her boyfriend; in Harry Potter and the Chamber of Secrets, she plays Moaning Myrtle, a young ghost who is always crying in the girls' room. In 2005 she was runner-up for the Golden Needle at the Seattle International Film Festival for Frozen (2004). In 2005 she won Best Actress at the Marrakech International Film Festival for Frozen (2004). In 2005 she was runner-up for Best Actress at the Film de Femmes Creteil for Frozen (2004). In 2004 she won a Best Scottish Actor nomination at the Glenfiddich Spirit of Scotland Awards. In 2004 she won the Bowmore/Scottish Screen/Sunday Times Actress of the Year for American Cousins (2003), intermission (2003) and Wilbur Wants to Kill Himself (2002). In 2004 she won Best Comedy Actress at the Newport Beach Film International Film Festival for American Cousins (2003). In 2003 she won the Silver Plaque at the Chicago International Film Festival for Fishy (2003). In 2001 she won a nomination for the Bowmore/Scottish Screen/Sunday Times Actress of the Year for Wonderland (1999) and Topsy-Turvy (1999). In 2002 she won a nomination for the Bowmore/Scottish Screen/Sunday Times Actress of the Year for The Claim (2000) and Bridget Jones's Diary (2001). In 2002 she was named Most Deserving Actor by The Scotsman newspaper for Twenty-four Hour Party People (2002), Once Upon a Time in the Midlands (2002), Villa des Roses (2002) and Harry Potter and the Chamber of Secrets (2002). In 2003 she won a nomination for the Bowmore/Scottish Screen/Sunday Times Actress of the Year for Twenty-four Hour Party People (2002), Once Upon a Time in the Midlands (2002), Villa des Roses (2002) and Harry Potter and the Chamber of Secrets (2002). In 2003 she won a British Supporting Actress of the Year nomination at the London Film Critics Circle for Twenty-four Hour Party People (2002). In 2005 she was awarded Best Actress in a Scottish Film by the BAFTA Awards Scotland for Frozen (2004). In 2006 she won Best Actress at the Cherbourg International Film Festival for Frozen (2004).