Wilson played college football for the NC State Wolfpack and was selected by the Arizona Cardinals in the third round of the 2001 NFL draft.

Head coach Dave McGinnis named Wilson the backup strong safety to start the regular season, behind Pat Tillman.

[9] On January 6, 2002, Wilson broke up a pass and returned an interception by quarterback Tony Banks for a 61-yard touchdown in a 20–17 loss at the Washington Redskins in Week 17.

[9] He finished his rookie season in 2001 with 32 combined tackles (24 solo), six passes defensed, two interceptions, a touchdown, and was credited with a half a sack in 16 games and zero starts.

[10] Wilson entered training camp slated as the starting strong safety after the role was left vacant by the departure of Pat Tillman.

On October 20, 2002, Wilson collected eight combined tackles, deflected three passes, made a season-high three interceptions, and recorded his first career sack in the Cardinals' 9–6 victory against the Dallas Cowboys in Week 7.

[17] On September 19, 2004, Wilson recorded a season-high 11 combined tackles (ten solo) and two pass deflections during a 23–12 loss to the New England Patriots.

[21] On November 13, 2005, he collected a season-high 14 combined tackles (ten solo) and two pass deflections in a 29–21 loss at the Detroit Lions in Week 10.

[21] In Week 16, Wilson recorded five solo tackles, a pass deflection, and made two sacks on quarterback Donovan McNabb in the Cardinals' 27–21 win against the Philadelphia Eagles.

[10] Head coach Dennis Green retained Wilson and Robert Smith as the starting safety duo to begin the season in 2006.

[22] On October 1, 2006, Wilson recorded five combined tackles, a pass deflection, and returned an interception by quarterback Michael Vick for a 99-yard touchdown as the Cardinals lost 32–10 at the Atlanta Falcons.

He finished the season with a total of 82 combined tackles (74 solo), seven pass deflections, five sacks, four interceptions, and a touchdown in 16 games and 16 starts.

[26] He started in the Arizona Cardinals' season-opener at the San Francisco 49ers and collected ten combined tackles (six solo) and a pass deflection in their 20–17 loss.

On November 28, 2007, the Arizona Cardinals placed Wilson on injured reserve for the remainder of the season after it was confirmed he would have to undergo surgery to repair a torn Achilles tendon and an injury he sustained to his right heel.

[29] Wilson completed his first season under Ken Whisenhunt with a total of 44 combined tackles (33 solo), three pass deflections, and two interceptions in nine games and nine starts.

[32] On January 18, 2009, Wilson collected seven solo tackles, deflected a pass, and made two sacks in a 32–25 victory at the Philadelphia Eagles in the NFC Championship Game.

[36] Defensive coordinator Billy Davis retained Wilson and Antrel Rolle as the starting safety duo to begin the regular season.

[37] On December 14, 2009, Wilson recorded a season-high eight solo tackles, a career-high five pass deflections, and an interception during a 24–9 loss at the San Francisco 49ers in Week 14.

On January 16, 2010, Wilson recorded nine combined tackles and a pass deflection during a 45–14 loss at the New Orleans Saints in the NFC Divisional Round.

[43] On January 6, 2011, Arizona Cardinals' head coach Ken Whisenhunt fired defensive coordinator Bill Davis after the team finished with a 5–11 record in 2010.

[44] Their new defensive coordinator, Ray Horton, retained both Wilson and Kerry Rhodes as the starting safety tandem to begin the regular season.

[48] In Week 4, he collected a season-high ten combined tackles (eight solo), three pass deflections, a forced fumble, and sacked quarterback Ryan Tannehill during a 24–21 overtime victory against the Miami Dolphins.

[49] On December 16, 2012, Wilson recorded three solo tackles and sacked quarterback Matthew Stafford during a 38–10 win against the Detroit Lions in Week 15.

[50] He completed his last season with the Cardinals with a total of 54 combined tackles (39 solo), five pass deflections, three sacks, a forced fumble, and an interception in 15 games and 14 starts.

[10] On January 3, 2013, the Arizona Cardinals fired general manager Rod Graves and head coach Ken Whisenhunt after they did not qualify for the playoffs after finishing with a 5–11 record in 2012.

[61] On February 27, 2023, Wilson left the Cardinals in favor of the Carolina Panthers, assuming the role of Vice President of Player Personnel.