Masterson played Geoff in the direct-to-video movie Dragonheart: A New Beginning, the sequel to Dragonheart. Masterson is best known for playing the character of trouble-making Francis in the sitcom Malcolm in the Middle. He took on the role for seven years, from 2000–2006. In 2003 he played Edward Linton in MTV's Wuthering Heights. Masterson portrayed a lead character in the films Scary Movie 2, Waterborne, Made for Each Other and Intellectual Property. He guest starred in two episodes of That '70s Show, alongside his brother, Danny. In the USA Network television series White Collar, he played Josh Roland in the episode "Where There's a Will". He also played Scotty O'Neal in the movie My Best Friend's Wedding. In 2012, Masterson had a guest role on the TBS series Men at Work as a concierge named Archie. His brother, Danny Masterson, plays Milo on the show, but the two did not share any scenes together.