He played college football for Penn State Nittany Lions, and was signed by the New York Giants as an undrafted free agent in 2005.

Wake has also played for the CFL's BC Lions, earning the league's Most Outstanding Rookie Award in 2007.

He recorded 39 sacks over his first two seasons in the CFL, earning Western Division All-Star honors as well as the Most Outstanding Defensive Player Award both years.

[citation needed] Prior to the 2005 NFL draft, Wake worked out at Penn State's Pro Day and ran a 4.55-second 40-yard dash.

[8] Wake signed a free agent contract with the BC Lions of the Canadian Football League in May 2007.

Switching from linebacker to defensive end, a rejuvenated Wake had an immediate impact with the team, and was named the Defensive Player of the Week for the first week of the 2007 CFL season after an impressive debut (7 tackles, 3 quarterback sacks) in a 24–22 Lions' victory over the Toronto Argonauts.

[12] In 2008, Wake was also named TSN's Friday Night Gladiator of the Year, the first defensive player to win the award.

At the end of the 2008 CFL season, Wake drew interest from several NFL teams, including the Miami Dolphins, St. Louis Rams, New Orleans Saints, Buffalo Bills and Minnesota Vikings.

[16] After receiving interest from 17 total NFL teams and working out for eight, Wake signed with the Dolphins on January 18, 2009.

[7] Wake started the first game of his NFL career during the 2009 season against the Bills in Week 4 and responded with two sacks, four tackles for a loss, and a forced fumble.

[23] Wake sacked Bengals quarterback Andy Dalton in overtime for a safety to end the game, giving the Dolphins a 22–20 victory.

Wake returned to his dominant form, recording six sacks and four forced fumbles in a two-week span, which were both wins against the Titans and Texans.

In a game against the Patriots, Wake notched his seventh sack, which put him in second place on the NFL leaderboard, but he was also injured and carried off the field on a later play.

[29] On February 18, 2017, Wake signed a two-year contract extension with the Dolphins through the 2018 season, worth up to $18 million.