In football, he was a two-way player as quarterback and defensive back, and helped his team to a perfect 15–0 record and the SCHSL AAAA Division II title as a senior.

[6] On March 28, 2012, Gilmore attended South Carolina's pro day, along with Alshon Jeffery, Antonio Allen, Melvin Ingram, and 11 other prospects.

[17] Gilmore made his NFL debut and first career start in the Bills' season-opener at the Jets and recorded five combined tackles during a 48–28 road loss.

On December 9, Gilmore collected two combined tackles and recorded his first NFL interception off of Sam Bradford during a 15–12 loss to the St. Louis Rams.

On August 26, head coach Doug Marrone announced Gilmore suffered a fractured wrist, had undergone surgery, and was expected to miss 6–8 weeks.

During Week 14, Gilmore made two combined tackles, two pass deflections, and intercepted Mike Glennon during a 27–6 road loss to the Tampa Bay Buccaneers.

[22] Gilmore finished his second season with 35 combined tackles (30 solo), ten pass deflections, and two interceptions in 11 games and nine starts.

During Week 8, Gilmore collected five combined tackles, deflected a pass, and intercepted quarterback Geno Smith during a 43–23 road victory over the Jets.

[30] New head coach Rex Ryan named Gilmore and Ronald Darby the starting cornerback duo to begin the regular season.

During Week 5 against the Tennessee Titans, he recorded a solo tackle, a career-high four pass deflections, and an interception during a narrow 14–13 road victory.

[32] On December 16, Gilmore was placed on injured reserve for the rest of the season after he underwent surgery the previous day to repair his torn labrum.

[33] Gilmore finished his first season under defensive coordinator Dennis Thurman with 36 solo tackles, a then career-high 18 pass deflections, and three interceptions in 12 games and starts.

In the next game, he made three combined tackles, four pass deflections, and intercepted Arizona Cardinals' quarterback Carson Palmer twice in their 33–18 victory.

[37] During Week 11, he made six combined tackles, three pass deflections, and intercepted quarterback Andy Dalton twice during a 16–12 road victory over the Bengals.

[38] On December 27, the Buffalo Bills fired head coach Rex Ryan after losing to the Miami Dolphins and falling to a 7–8 record.

Gilmore finished his first season with the Patriots with a career-high 50 combined tackles (47 solo), nine pass deflections, and two interceptions in 13 games and starts.

On January 13, 2018, Gilmore started in his first NFL playoff game and recorded one tackle and two pass deflections as the Patriots defeated the Titans by a score of 35–14 in the AFC Divisional round.

After defeating the Jacksonville Jaguars in the AFC Championship Game by a score of 24–20, the Patriots went on to face the Philadelphia Eagles in the Super Bowl.

[51][52][53] On February 4, 2018, Gilmore started in Super Bowl LII and recorded four solo tackles and two pass deflections during the Patriots' 41–33 loss to the Eagles.

During the season-opener, Gilmore recorded a season-high eight combined tackles, two pass deflections and intercepted Deshaun Watson in a 27–20 win over the Texans.

[58] During Super Bowl LIII against the Los Angeles Rams, Gilmore intercepted a fourth quarter throw from quarterback Jared Goff that was intended for former teammate Brandin Cooks to seal a 13–3 victory for the Patriots.

During Week 2 against the Dolphins, Gilmore intercepted former teammate Ryan Fitzpatrick and returned it for a 50-yard touchdown as the Patriots won on the road by a score of 43–0.

[60] In Week 6 against the New York Giants, Gilmore recorded five pass deflections and a toe tapping interception off of Daniel Jones on the sideline in the 35–14 victory.

[74] In the next game against the Seattle Seahawks, he struggled to cover wide receiver DK Metcalf allowing 92 yards including a 54-yard touchdown in the 30–35 road loss.

[80] On October 6, 2021, Gilmore was traded to the Carolina Panthers, after the Patriots couldn't rework his contract, in exchange for a sixth-round selection (#187-Kayshon Boutte) in the 2023 NFL draft.

On March 14, 2023, the Colts traded Gilmore to the Cowboys in exchange for a compensatory fifth round selection (#176-Evan Hull) in the 2023 NFL Draft.

[85] His dependable play and leadership skills, helped the team withstand the loss of All-Pro cornerback Trevon Diggs to a season-ending torn left ACL injury after two games.

Gilmore suffered a torn labrum injury in the season finale against the Washington Commanders, which caused him to struggle in the 32-48 Wild Card playoff loss against the Green Bay Packers.

He started in all 17 regular season games, finishing with 68 total tackles (54 solo), two interceptions, 13 passes defended, and one forced fumble.

[89] Gilmore has a younger brother named Steven who played cornerback for Marshall[90] and spent some time on the Detroit Lions roster.