Before playing the role of Dr. Owen Hunt in Grey's Anatomy, for which he is widely known, McKidd appeared as Tommy Mackenzie in Danny Boyle's Trainspotting (1996).

In 2004, he played James Hepburn, 4th Earl of Bothwell, the third husband of Mary, Queen of Scots, in the BBC mini-series Gunpowder, Treason & Plot.

In 1999, he was part of an ensemble cast in Mike Leigh's Topsy Turvy, depicting the development of Gilbert and Sullivan's The Mikado.

The actors researched their historical characters and used this knowledge during extensive rehearsals to help develop dialogue for scenes blocked out by Leigh.

He was also one of the main stars of the joint HBO/BBC series Rome, where his portrayal of the soldier-politician Lucius Vorenus received critical acclaim.

In late 2007, McKidd began his role as the lead character in the American fantasy television series Journeyman on NBC.

[8] Despite starting out with a strong audience, the show lost about half of its viewership throughout its run and suffered from the fractious situation in the United States due to the writer's strike at the time.

His role in Rome led to McKidd's casting in the medical drama series Grey's Anatomy as Dr. Owen Hunt.

McKidd has done voice work and voiced the character of Jezz Torrent, flame haired lead singer of the fictional Scottish hard rock band Love Fist in the video game Grand Theft Auto: Vice City.

McKidd instigated The Speyside Sessions, a Scottish folk music album recorded in 2011/12 at Hogmanay in his home town of Elgin.

Of Scottish independence, McKidd stated, "A lot of people think we're all gonna fall flat on our face if we do this.