His professional film career began when he played Flash Thompson in Sam Raimi's Spider-Man. His breakout role was as werewolf Alcide Herveaux in five seasons of the HBO series True Blood.

He is also known for his roles in films such as Magic Mike, Magic Mike XXL, Pee-wee's Big Holiday, What to Expect When You're Expecting, Sabotage and Rampage. In late 2013, he became a published author when his first book, Evolution, was released by Simon & Schuster's Gallery Books.[1] His directorial debut came in 2014 with the documentary feature La Bare, which he also produced and financed. He is also known for his role as Brad Morris in How I Met Your Mother. He is active with several charities, primarily UPMC Children's Hospital of Pittsburgh for which he serves on the board of trustees. In 2016, he was cast as Slade Wilson / Deathstroke in the DC Extended Universe, making his first appearance in 2017's Justice League.