He made his film debut in 2006 with a small role in Talladega Nights: The Ballad of Ricky Bobby which was filmed primarily in and around Charlotte, North Carolina. That was soon followed by a role in the somewhat controversial movie Hounddog which was shot on a plantation near Wilmington, North Carolina. Much of the film's controversy stemmed from a pivotal scene in which a young girl, played by then 12-year-old Actress Dakota Fanning, was raped by Sanders' character. It was a role he found to be challenging, but one that gave him a chance to prove the range of his acting ability. When asked about the controversial scene, Sanders responded, "That's just one part of the film. Tragedies like that happen every day in real life, and I think that if this film opens a few more eyes, then it is definitely worth it. Movies can have that power."

In January 2007, he moved to Los Angeles where there would be more opportunities to pursue acting full-time. He got a part in a TV pilot within three months of being in Hollywood, but the show wasn't picked up by the network. He spent the next several months auditioning before landing a part in the movie Legally Blondes and the role of Ned Banks on Ghost Whisperer. He took over the role of Ned, which was previously held by Tyler Patrick Jones, when producers decided to age the character by few years in order to explore more mature storylines. This was only a recurring guest role in season three, but due to the character's popularity, Sanders became a part of the regular cast at the beginning of season four.