In January 2007, he first appeared in Waterloo Road for the BBC, playing sixth former Brett Aspinall. Despite being 24 at the time, Payne portrayed a 17-year-old character. He remained in the series until the end of the following season in March 2008. It was revealed afterward that he would not be returning for the new season, beginning in January 2009.
In 2009, Payne played George Best in Best: His Mother’s Son, a BBC 2 film about the legendary footballer. In the same year he appeared in Marple: They Do It With Mirrors and Wuthering Heights for ITV.
Payne was named as one of Screen International’s Stars of Tomorrow 2007.
On 8 March 2010, it was announced that Tom had joined the cast of Luck a new pilot for HBO directed by Michael Mann, written by David Milch, starring Dustin Hoffman and Nick Nolte. He plays the role of a Cajun jockey.
In 2012, he was cast in the title role of The Physician (based on the book of the same name) alongside Stellan Skarsgard and Ben Kingsley.
Payne was cast with a recurring role in Season 6 of The Walking Dead, as Paul “Jesus” Rovia, and promoted to series regular for season 7 but Jesus was killed off in season 9.