Born and brought up in Hemel Hempstead, Skinner, the youngest daughter of a shopkeeper and an Irish-born secretary, was immensely shy as a child. Skinner's childhood dream was to become an actress and she completely immersed herself in achieving her ambition. She acted all the time, neglecting all of her school work, at Cavendish School in Hemel Hempstead, and "barely scraped through my A-levels". She went on to study at the London Academy of Music and Dramatic Art and then later on joined the Royal Shakespeare Company.

Her first role was in Hanky Park, by Walter Greenwood at the Oldham Repertory Theatre, which she describes as a "really traditional start."

Skinner is best known for her starring role as Clare in the British TV comedy Life Begins and more recently as Sue in the BBC's Outnumbered. For many years, Skinner has preferred theatre to screen roles because she's been disappointed with her TV projects ("apart from Mike Leigh's stuff"), "not just when you see the final thing, but also because it hasn't taken off."

Skinner has worked with some of the stage and screen directors which include Mike Leigh, Trevor Nunn, Tim Burton and Sam Mendes, but she remembers one particular director, Alan Ayckbourn, when she first started out: "He was a great influence for me as he pushed me so hard, but every director you work with has a big influence in some way, they really push you.”

She is married to director Charles Palmer, the son of actor Geoffrey Palmer.