Indianapolis Colts Hughes was selected in the first round by the
Indianapolis Colts 31st overall in the 2010 NFL Draft. He is the first TCU Horned Frog selected in the first round of an NFL Draft since
LaDainian Tomlinson went fifth overall to the
San Diego Chargers in the
2001 NFL draft, and the first TCU defensive player selected in the first round since
Bob Lilly, who was selected 13th overall by the
Dallas Cowboys in the
1961 NFL draft. During his rookie season, Hughes appeared in 12 games making six tackles. In 2011, Hughes appeared in 12 games with one start making 13 tackles and one sack. On November 16, 2012, Hughes was fined $21,000 for a late hit against the
Jacksonville Jaguars in Week 10. He finished the 2012 season by appearing in all 16 games with six starts recording 32 tackles, one pass defended, and four sacks.
Buffalo Bills in 2021 On April 29, 2013, the Colts traded Hughes to the
Buffalo Bills for linebacker
Kelvin Sheppard. Hughes finished his first season with the Bills by making 46 tackles, 10 sacks and two forced fumbles in 16 games with one start. He was also named to the USA Today All-Joe Team. On March 9, 2015, the Buffalo Bills and Hughes agreed to a five-year contract worth at least $45 million. He played through the majority of the 2015 season with a chipped bone in his left wrist as a hybrid LB/DE . In 2016, as the Bills more fully committed to a 3-4 scheme, Hughes was moved from defensive end to outside linebacker. On May 21, 2019, Hughes signed a two-year contract extension with the Bills. In the AFC wild card game against the
Houston Texans, Hughes sacked quarterback
Deshaun Watson 3 times during the 22–19 overtime loss. In Week 7 of the 2020 season against the
New York Jets, Hughes recorded six tackles, two sacks, a forced fumble, and the game sealing interception late in the fourth quarter during the 18–10 win, earning AFC Defensive Player of the Week. In Week 15 against the
Denver Broncos, Hughes recovered a fumble forced by teammate
Tre'Davious White on
Drew Lock and returned it for a 21 yard touchdown during the 48–19 win. In the Divisional Round of the playoffs against the
Baltimore Ravens, Hughes recorded two sacks on
Lamar Jackson during the 17–3 win. In the AFC Championship against the
Kansas City Chiefs, Hughes recorded one sack on
Patrick Mahomes during the 38–24 loss. By the 2021 season, Hughes became the longest tenured player on the Bills' roster. A free agent after the season, he finished his 9-year tenure with Buffalo having amassed 53 sacks, ranking 4th in team history at the time.
Houston Texans On May 11, 2022, Hughes signed with the Texans. He started 16 games and led the team with nine sacks. He returned in 2023 to record 32 tackles and three sacks in 17 games and two starts. On July 9, 2024, Hughes re-signed with the Texans after initially entering free agency. ==NFL career statistics==