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In 1983, Firth starred in the award-winning London stage production of Another Country, and reprised his role for his first film appearance in 1984. 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 took the lead 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) and Bridget Jones: The Edge of Reason (2004). He has also appeared in recent television productions, including Donovan Quick (an updated version of Don Quixote) (1999) and Conspiracy (2001). In 2007, Firth starred with Aishwarya Rai in The Last Legion.

Firth is also a Jury Member for the on going Filmaka amateur short film contest.

In 1989, Firth entered into a romantic relationship with actress Meg Tilly his co-star in Valmont. In 1990, she gave birth to a son, Will Firth. In 1994, Firth was involved with actress Jennifer Ehle, his co-star in Pride and Prejudice. Firth lives both in London and Italy and is currently married to an Italian film producer/director Livia Giuggioli. They have two sons, Luca (born March 2001) and Matteo (born August 2003).

Recently, Firth has been involved in a campaign to stop the deportation of a group of asylum seekers, because he believes that they may be murdered on their return to the Democratic Republic of Congo.[15] Firth has argued that "To me it's just basic civilisation to help people. I find this incredibly painful to see how we dismiss the most desperate people in our society. It's easily done. It plays to the tabloids, to the Middle-England xenophobes. It just makes me furious. And all from a government we once had such high hopes for".[16] As a result of the campaign, a Congolese nurse was given a last-minute reprieve from deportation.[17]

Firth has also been a long-standing supporter of Survival International, a charity which defends the rights of tribal peoples.[18] Speaking in 2001, he said, "My interest in tribal peoples goes back many years... and I have supported [Survival] ever since."[19]

In a 2006 interview with French magazine Madame Figaro,[20] Firth was asked "Quelles sont les femmes de votre vie?" (Who are the women in your life?). Firth replied: "Ma mère, ma femme et Jane Austen" (My mother, my wife and Jane Austen).

Firth was awarded an honorary degree on 19 October 2007 from the University of Winchester.