In his senior season, Derek Wolfe was named Co-Big East Defensive Player of the Year. Derek Wolfe was selected with the 36th overall pick in the second round of the 2012 NFL Draft by the Denver Broncos. Derek Wolfe made his NFL debut with the Denver Broncos on August 9, 2012 in a preseason game against the Chicago Bears where he had two sacks and three tackles. Derek Wolfe finished his rookie season with 40 tackles, six sacks, and two passes defensed. His six sacks were the third most on the team behind Von Miller and Elvis Dumervil.