As a senior, he registered 22 receptions for 400 yards, 5 touchdowns, 77 tackles, one interception and 3 forced fumbles, while helping the Cairo Syrupmakers win the 2008 state championship.

Under Detroit Lions' head coach Jim Schwartz, he had impressive performances in practice during the week leading up to the Senior Bowl.

[12] He competed with Will Allen, Jeff Heath, Matt Johnson, and Brandon Underwood for the job as the starting free safety left by the departure Gerald Sensabaugh.

[13] The Dallas Cowboys were going to name him starting free safety during training camp, but the unexpected death of his mother slowed his progress due to a two-week absence.

Head coach Jason Garrett decided to name veteran Will Allen the starter instead to start the regular season instead.

[14] He made his professional regular season debut in the Dallas Cowboys' season-opener against the New York Giants and assisted on one tackle during their 36–31 win.

On September 22, 2013, Wilcox earned his first career start at free safety and recorded three combined tackles in the Cowboys' 31–7 victory over the St. Louis Rams.

The injury occurred during red zone drills as he was defending a pass against tight end Gavin Escobar[16] During his absence, he was replaced by rookie undrafted free agent Jeff Heath.

[18] He finished the year in a reserve role at free safety and had a total of 38 combined tackles (22 solo) and a pass deflection in 13 games and five starts.

On October 27, 2014, Wilcox collected seven solo tackles and made his first career interception off a pass attempt by Washington Redskins' quarterback Colt McCoy during a 20–17 overtime loss.

On January 4, 2015, Wilcox started his first career playoff game and recorded seven solo tackles in a 24-20 NFC Wildcard championship victory over the Detroit Lions.

There was major controversy surrounding the ending of the game after Dez Bryant's 31-yard catch on a fourth and two was overturned after a challenge by Packers' head coach Mike McCarthy.

[23] He started 16 games and was fourth on the team with 74 combined tackles (62 solo), three interceptions, four pass deflections, one forced and two fumble recoveries.

[25] Wilcox started the Dallas Cowboys' season-opener against The New York Giants and recorded three combined tackles and defended a pass in their 27–26 victory.

During the first quarter, Wilcox delivered a vicious hit against Giants' wide receiver Odell Beckham Jr. and successfully broke up a pass attempt by Eli Manning.

Philadelphia Eagles' quarterback Sam Bradford completed a pass to Jordan Matthews who scored a 41-yard touchdown after Byron Jones stumbled and Wilcox took a poor angle while in pursuit.

During a Week 17 matchup against the Washington Redskins, Wilcox recorded two solo tackles and had the first safety of his career in the Cowboys' 34–23 loss.

Wilcox recorded the safety, along with DeMarcus Lawrence in the fourth quarter, stopping Redskin' running back Alfred Morris in the endzone.

[35][36] Wilcox entered training camp on the roster bubble after losing his starting free safety job to Byron Jones after a difficult 2015 season.

[30] Head coach Jason Garrett named Wilcox the backup strong safety to Barry Church to start the 2016 season.

[24] In Week 9, Wilcox returned to the starting lineup at the Cleveland Browns after Barry Church fractured his arm the game prior against the Philadelphia Eagles.

During a Week 12 contest against the Washington Redskins, Wilcox recorded four solo tackles, but left the Cowboys' 31–26 victory after suffering a thigh contusion.

[41] Throughout training camp, Wilcox competed with Chris Conte, Keith Tandy, and Justin Evans for a job as one of the starting safeties, but struggled and was projected as a reserve player.

[42] On September 3, the Pittsburgh Steelers acquired Wilcox in a trade with the Tampa Bay Buccaneers to improve their depth at safety, following injuries to Jordan Dangerfield and Mike Mitchell.

He delivered a helmet-to-helmet hit on Browns' wide receiver Corey Coleman in the fourth quarter and was knocked unconscious in the process.

[59] His father previously played running back for Fort Valley State and had an invitation to attend training camp with the Miami Dolphins.