Firth was born the son of Shirley Jean (née Rolles), a comparative religion lecturer, and David Norman Lewis Firth, a history lecturer and education officer for the Nigerian Government.

Firth has a sister, Kate, and a younger brother, Jonathan, who is now also an actor. Firth's parents were born and raised in India, because his maternal grandparents, Congregationalist ministers, and his paternal grandfather, an Anglican minister, performed missionary work abroad.

Firth spent part of his childhood in Nigeria, where his father was teaching. He lived in St. Louis, Missouri when he was 11. He later attended the Montgomery of Alamein Secondary School, a state comprehensive school in Winchester, Hampshire, and then Barton Peveril College in Eastleigh, Hampshire. His acting training took place at the Drama Centre in North London.

In 1983, Firth starred as Guy Bennett in the award-winning London stage production of Another Country. In 1984, he made his film debut in the screen adaptation of the play, taking the role of Tommy Judd (opposite Rupert Everett as Bennett). In 1987, he appeared alongside Kenneth Branagh in the film version of J. L. Carr's novel, A Month in the Country. In 1989, he played the title role in the film Valmont.

Following these earlier roles, it was in the 1995 BBC television adaptation of Jane Austen's classic Pride and Prejudice that Firth gained wider renown. The serial was a major international success, and Firth became known as a heartthrob because of his role as Fitzwilliam Darcy.

This performance also made him the object of affection for fictional journalist Bridget Jones (created by Helen Fielding), an interest which carried on into the two novels featuring the Jones character. In the second novel, Bridget Jones: The Edge of Reason, the character even meets Firth in Rome.

As something of an in-joke, when the novels were adapted for the cinema, Firth was cast as Jones's love interest, Mark Darcy. Continuing this in-joke there was a dog called Mr Darcy in the film St. Trinian's which Colin's character accidentally kills.

Firth had a supporting role in The English Patient (1996) and since then has starred in films such as Fever Pitch (1997), Shakespeare in Love (1998), Bridget Jones's Diary (2001), The Importance of Being Earnest (2002), Love Actually (2003), What a Girl Wants (2003), Bridget Jones: The Edge of Reason (2004), Nanny McPhee (2005), The Last Legion with Aishwarya Rai (2007), and the film adaptation of Mamma Mia! (2008).

He has also appeared in recent television productions, including Donovan Quick (an updated version of Don Quixote) (1999) and Conspiracy (2001), for which he received an Emmy nomination.