During the 2010 season, Wake had a memorable Week 6 against the Packers. He had three sacks, including one on third down in overtime, bringing his total to six sacks in five games, already surpassing his total the previous year of 5½ sacks with limited playing time. He ended a game against the Jets with a sack on quarterback Mark Sanchez completing his second of the game. Wake would lead the NFL in sacks at one point and eventually finish third in the NFL (second in the AFC) in sacks. By the end of the season, Wake had recorded 14 sacks, 57 tackles, and three forced fumbles.