Masterson started out in the business as a child model and landed a role on family film Beethoven 2. He also starred as the beloved "Steven Hyde" in the hit Television series That 70`s Show. Masterson was also a DJ at Los Angeles Alternative Rock Station KDLD Indie 103.1.
Following the conclusion of That 70's Show, Masterson starred in the Jim Carrey comedy Yes Man, the TBS sitcom Men at Work, and the Netflix comedy-drama The Ranch (alongside Ashton Kutcher). In December 2017 Masterson was fired from The Ranch, after rape allegations were filed from four women.
His siblings are actors as well, brother Christopher Masterson and half-siblings Jordan and Alanna Masterson. He is married to Bijou Philips.