Colvin started her career a year after graduating from Yale as a midnight-to-6 a.m. police reporter for United Press International in New York City.[5] In 1984, Colvin became the Paris bureau chief for United Press International, moving to The Sunday Times in 1985. Starting in 1986, she was the newspaper's Middle East correspondent, and then from 1995 was the Foreign Affairs correspondent. In 1986, she was the first to interview Muammar Gaddafi after Operation El Dorado Canyon.[6] Although specializing in the Middle East, she also covered conflicts in Chechnya, Kosovo, Sierra Leone, Zimbabwe, Sri Lanka and East Timor. She won the International Women's Media Foundation award for 'Courage in Journalism' for her coverage of Kosovo and Chechnya.[7][8][9] She wrote and produced documentaries, including Arafat: Behind the Myth for the BBC.[10] She is featured in the 2005 documentary film Bearing Witness.

She began wearing an eyepatch after losing the sight in her left eye when coming under Sri Lankan government RPG shrapnel fire on April 16, 2001; she was attacked after calling out "journalist, journalist!" while reporting on the Sri Lankan Civil War.[11][12][13][14] Colvin was also a witness and an intermediary during the final days of the war in Sri Lanka and reported on war crimes that were committed during this phase.[14]

In 2011, while reporting on the Libyan civil war, she was offered an opportunity to interview Muammar Gaddafi, along with two other journalists that she could nominate. The first international interview since the start of the war, she took along her friends Christiane Amanpour of ABC News[15] and Jeremy Bowen of BBC News.[16]