Born in Oregon, he was cast as Skeet on MTV's Undressed before landing his breakthrough role as Brad O'Keefe on Grounded for Life, a show he became a part of from 2001 to 2005. Subsequently, he played the role of Danny on The O.C., Charlie Richardson on That '70s Show and as Sam Sullivan on The Loop.
In 2007, Harrison was cast as the lead in the comedy Reaper, playing a reaper who works for the devil. The show, which ran for only two seasons, also featured Ray Wise and Missy Peregrym. He later joined the cast of ABC's V as Dr. Sidney Miller, and as Cameron Price on FOX's Breaking In, opposite Christian Slater. Though the latter was cancelled twice, it was renewed for a second season in 2012. Harrison is also known for his music. He is part of the four-piece indie rock band Big Japan, which also features actor Adam Brody.