He played college football for the Florida State Seminoles and was selected by the Buffalo Bills in the second round of the 2015 NFL draft.

A world-class sprinter during his high school years, Darby won medals at the 2011 World Youth Championships in Athletics.

Darby attended Potomac High School in Oxon Hill, Maryland, where he played as many as six different positions on offense, defense, and special teams.

Excelling on defense, Darby was part of a Wolverines' secondary that also included Tavon Young, and which registered four shutouts and allowed just 82 points in 2011.

[2][3] He also finished fourth in the 100 m.[4] Along with Aldrich Bailey, Najee Glass, and Arman Hall, he ran a World Youth Best in the meet's medley relay.

Additionally, Darby was a brother of Pi Kappa Alpha fraternity while attending Florida State University.

[6] Although exclusively a back-up to Xavier Rhodes and Nick Waisome, Darby registered 18 tacklesp and broke up seven passes in 2012, which earned him ACC Defensive Rookie of the Year honors.

[10] Coming out of Florida State, Darby was projected to be selected in the second or third rounds by the majority of analysts and scouts.

He had scheduled visits with the Tampa Bay Buccaneers, Indianapolis Colts, Carolina Panthers, Tennessee Titans, and New York Jets.

[22] On September 27, 2015, he made five combined tackles and a season-high four pass deflections, and intercepted Miami Dolphins' quarterback Ryan Tannehill during a 41–14 victory.

He started the Bills' season-opener against the Baltimore Ravens and recorded seven solo tackles and made three pass deflections in a 13–7 loss.

[26] The Bills finished with a 7–9 record and head coach Rex Ryan was fired after Week 16 and replaced with Anthony Lynn.

On August 11, 2017, the Bills traded Darby to the Philadelphia Eagles for slot wide receiver Jordan Matthews and a third round pick (96th overall) in the 2018 NFL draft.

[36] In week 13 against the Miami Dolphins, Darby intercepted a pass thrown by Ryan Fitzpatrick on the first drive of the game in the 37–31 loss.

[44] On August 18, 2023, Darby signed with the Baltimore Ravens following an injury to their All-Pro corner Marlon Humphrey.