He is also known for his significant supporting roles in films such as The Curious Case of Benjamin Button (2008), Sherlock Holmes: A Game of Shadows (2011), and Hari Seldon, a leading character in the science fiction series Foundation (2021).

He took minor roles in films such as the western romance Far and Away (1992), the historical epic The Last of the Mohicans (1992), and the crime drama Natural Born Killers (1994).

That same year he portrayed Vladimir in the controversial black comedy drama film Happiness (1998), written and directed by Todd Solondz.

"[7] Harris received critical acclaim for his final appearance in the episode "Commissions and Fees" as well as a nomination for the Primetime Emmy Award for Outstanding Supporting Actor in a Drama Series, losing to Aaron Paul for Breaking Bad in 2012.

[8] His portrayal of King George VI in the first season of The Crown received praise from critic Matt Zoller Seitz, who stated that despite the series' large ensemble, "Harris still manages to communicate the character’s understated sensitivity and awareness of his circumscribed role in England’s drama so poignantly that one can’t help being moved by the performance".

He portrayed Captain Francis Crozier in the 2018 series The Terror, based on the Dan Simmons novel of the same name that provided a fictional account of the fate of Franklin's lost expedition.

Harris said that he was "gratified" that the series inspired curiosity about the real expedition, remarking, "It’s sort of fitting that history will recall that it was the RCGS that first recognized The Terror, and that we as the recipients walked in the footsteps of Louie Kamookak.

[12] He plays the developer of psychohistory Hari Seldon in the Foundation television series produced for Apple TV+ which premiered in September 2021.

[14] In 2024, he played the father of a returning missing child in the British psychological thriller film Reawakening, alongside Erin Doherty and Juliet Stevenson.

In April 2009, Harris met Allegra Riggio, a lighting designer and television host,[19] at a comedy club where a mutual friend was performing.