Clayton played three years of football at Auburn High School in Auburn, Alabama, as well as excelling in the discus and shotput for the 9-time state champion Tigers. Midway through his junior season a move required him to transfer to rival Opelika High School in Opelika, Alabama, where he finished his high school career in 2006. He was named to the Alabama Sports Writers Association 6A All-State Team as a senior.
Clayton redshirted his freshman year at Auburn in 2006, and saw action in 10 games in 2007. He started one game in 2008, totaling 22 tackles and finished 15th in the SEC in sacks per game as a sophomore. Clayton's junior season in 2009 was marred by injury and he only played in six games, with seven tackles on the season. 2010 saw Clayton start all 14 games, with 28 tackles (8 tackles for loss), including three tackles and one sack in the 2011 BCS National Championship Game vs. the Oregon Ducks.