He played college football for the Temple Owls, and was selected by the New York Jets in the first round of the 2011 NFL draft.

In 2017, Wilkerson's relationship with the franchise soured due to violations of team rules, leading to his release after the season.

[1] He was selected to the Home News Tribune all-area first-team and Newark Star Ledger all-Union County second-team.

[9][10] He was the fourth Temple player to be drafted by the Jets, preceded by Mike Stromberg, Joe Klecko and Dave Yovanovits.

[13] During the third preseason game against the New York Giants, Wilkerson got into a fight with running back Brandon Jacobs, resulting in both players getting ejected.

[15] Wilkerson started all 16 games in 2011 making 49 tackles with 3 sacks, 2 passes defended, 1 forced fumble, and 1 safety enforced.

During a game against the Seattle Seahawks on November 11, 2012, Wilkerson scooped up a fumble lost by Russell Wilson and returned it for a touchdown.

During Week 17 against the Buffalo Bills on January 3, 2016, Wilkerson suffered a broken leg and was carted off the field as the Jets lost the game 17–22 and were eliminated from playoff contention despite finishing the year with a 10–6 record.

[20] Wilkerson was selected for the 2016 Pro Bowl, but was unable to participate due to a right fibula fracture sustained during the Jets' final game of the season.

[23] On December 15, the Jets announced that Wilkerson would be scratched for the upcoming Week 15 game against the New Orleans Saints due to showing up late for a team meeting.

Wilkerson was carted off the field[30] and underwent surgery the same night in a Washington, D.C. hospital, causing him to miss the team flight back to Wisconsin.

[37] On March 4, 2020, it was revealed that Wilkerson was arrested by New Jersey State Police for DWI plus possession of marijuana and paraphernalia.