Fuller was a five-star recruit by Rivals.com and was ranked as the second best cornerback and ninth best player overall in his class. He committed to Virginia Tech in July 2012 to play college football.

As a true freshman in 2013, Fuller started 12 of 13 games, recording 58 tackles and six interceptions. For his play he was named the ACC Defensive Rookie of the Year. Fuller returned as a starter his sophomore season in 2014. On December 15, 2015, Fuller declared for the 2016 NFL Draft.

The Washington Redskins selected Fuller in the third round (84th overall) of the 2016 NFL Draft. Fuller was the 14th cornerback selected in 2016.

On June 2, 2016, the Washington Redskins signed Fuller to a four-year, $3.12 million contract that includes a signing bonus of $718,424.

He was inactive for the first three games (Weeks 1-3) and made his professional regular season debut in Week 4 after injuries to Bashaud Breeland and Quinton Dunbar. On October 2, 2016, Fuller earned his first career start and recorded a season-high eight combined tackles during a 31–20 victory against the Cleveland Browns. Fuller surpassed Greg Toler on the depth chart after Week 7 and became their fourth cornerback. In Week 8, he tied his season-high of seven solo tackles in the Redskins’ 27–37 tie at the Cincinnati Bengals. After struggling in Week 13, Fuller was replaced by Greg Toler after defensive coordinator Joe Barry demoted him to the fifth cornerback on the depth chart. He finished his rookie season in 2016 with 42 combined tackles (32 solo) and two pass deflections in 13 games and six starts.

On September 24, 2017, Fuller recorded three combined tackles, deflected a pass, and made his first career interception off a pass by Derek Carr during a 27–10 victory against the Oakland Raiders. In Week 6, he made a solo tackle, a season-high two pass deflections, and intercepted a pass by quarterback C. J. Beathard in the last ten seconds of the Redskins’ 26–24 victory against the San Francisco 49ers. On November 23, 2017, Fuller deflected a pass and recorded another victory-sealing interception against Eli Manning in the last 1:16 of the Redskins’ 20–10 victory against the New York Giants. In Week 15, he collected a season-high eight combined tackles and two pass deflections during a 20–15 win against the Arizona Cardinals. He finished the 2017 season with 55 combined tackles (43 solo), ten pass deflections, and four interceptions in 16 games and 16 starts.

On January 30, 2018, the Washington Redskins agreed to trade Fuller and a third round pick (78th overall) in the 2018 NFL Draft to the Kansas City Chiefs for quarterback Alex Smith. The trade was officially completed on March 14, the start of the new league year.

On December 14, 2018, Fuller underwent surgery on his wrist and was inactive for the Chiefs’ Week 16 loss at the Seattle Seahawks. He finished the season with 82 combined tackles (64 solo), 12 pass deflections, and two interceptions in 15 games and 15 starts.

On March 23, 2020, Fuller signed a four-year, $40 million contract with the Washington Football Team, formerly known as the Redskins. In Week 4 against the Baltimore Ravens, Fuller recorded his first two interceptions as a member of the Football Team from passes thrown by former Heisman Trophy winners Lamar Jackson and Robert Griffin III during the 31–17 loss.