Nicknamed The Freak Of Nature, Peppers played college football for the University of North Carolina, and was recognized as an All-American. The Carolina Panthers selected him with the second overall pick in the 2002 NFL Draft where he played his first eight seasons. He was named the 2002 AP NFL Defensive Rookie of the Year and was named the 2004 Defensive Player of the Year.

In 2010, the Chicago Bears signed Peppers to a six year contract. During week 17 against the Vikings in 2011, Peppers joined the 100 sacks club. He was released from the Bears in 2014 due to salary cap issues.