Prior to 2016, Wilson played a reserve role behind Vernon Hargreaves III, Brian Poole, and Teez Tabor.

[10] On March 28, 2017, Wilson attended Florida's pro day, but opted to stand on his combine numbers and only run coverage and receiving drills as scouts and team representatives from 28 NFL teams attended, including New England Patriots' head coach Bill Belichick.

[11] Wilson attended private workouts and visits with multiple teams, including the Dallas Cowboys, Philadelphia Eagles, and Cleveland Browns.

[12][13] At the conclusion of the pre-draft process, Wilson was projected to be a second round pick by NFL draft experts and scouts.

[21] Head coach Chuck Pagano named Wilson the third cornerback on the depth chart behind Vontae Davis and Rashaan Melvin.

[22] He made his professional regular season debut in the Colts' season-opener at the Los Angeles Rams and recorded one tackle in their 46–9 loss.

The following week, he earned his first career start in place of Vontae Davis, who missed the first three games due to a groin injury.

[25] He was named the starting cornerback along with rookie Nate Hairston after Melvin and Desir missed the remaining four games of the regular season.

In Week 17, he started his fourth consecutive game and recorded two solo tackles, a pass deflection, and made his first career interception on quarterback T. J. Yates in the Colts' 22–13 victory against the Houston Texans.

[26] He finished his rookie season in 2017 with 22 combined tackles (19 solo), six pass deflections, and an interception in seven games and five starts.

[27] The Indianapolis Colts finished third in the AFC South with a 4-12 record and head coach Chuck Pagano was fired after the season.