Birthistle was born in Bray, County Wicklow, Ireland, but moved with her family to Derry, Northern Ireland when she was 14. She was raised Catholic but attended the non-denominational Foyle College. After her GCSEs, she studied acting at The Gaiety School of Acting in Dublin.
She is best known for her role in Ae Fond Kiss... and since 2015 has starred in The Last Kingdom. She won the London Film Critics Circle British Actress of the Year Award in 2004, and has twice won the IFTA Best Actress in a Leading Role (Film) award.
- Brooklyn as Georgina (2015)
- The Children as Elaine (2008)
- Breakfast on Pluto as Eily Bergin (2005)
- Ae Fond Kiss as Roisin Hanlon (2004)
- Waking the Dead as Det Supt Sarah Cavendish (2011)
- Strike Back as Capt. Kate Marshall (2010-2011)
- Borstal Boy as Liz Joyce (2000)
- Trust as Maria Acklam (2003)
- Imagine Me & You as Edie (2005)
- Swansong as Karen Prince (2015)