Scott, the youngest of seven children, was born in Cottage Grove, Minnesota. He is the son of Patricia Anne (née Simons), a homemaker, and William Frank Scott, a factory worker. His eldest brother, Daniel, co-founded the Weekly Alibi after graduating from University of Wisconsin-Madison. Scott was inspired to become an actor while working at the local movie theater and seeing all the movies he could watch for free.
Scott's first commercial success came with the 1999 film American Pie, as Steve Stifler, a role he reprised in three sequels, American Pie 2 (2001), American Wedding (2003), and American Reunion (2012). For his supporting role in the first film, Scott was paid only $8,000. Scott was granted the lead role in American Wedding, though he only received second billing, and the character propelled him into the public consciousness. Scott's fear of typecasting led him to play different types of characters post-American Pie, such as a hapless nerd in the horror film Final Destination and a friendly stoner in Dude, Where's My Car?.
On March 16, 2011, Scott was admitted to a treatment facility for "health and personal issues". His representatives declined to confirm any details about the decision, including specifying the facility. On April 13, it was reported that Scott had successfully completed the treatment program.
In March 2012, Scott confirmed that he was engaged to model Lindsay Frimodt. In January 2013, US Weekly reported that this engagement had ended and that the two had split, but would remain friends.