After being moved from outside linebacker to defensive end for the 2012 season, Wake had arguably his best season in the NFL. He totaled 53 tackles and 15 sacks, including 4.5 sacks in one game against the Arizona Cardinals. That season, Wake was named a starter for the Pro Bowl for the second time and, together with Randy Starks, became the first of two Dolphins to make the Pro Bowl at two different positions. He was also named a First-Team All-Pro by both the AP and the PFWA for the first time in his career.