Simmons redshirted his first year at Clemson in 2016. As a safety in 2017, he played in 14 games, recording 49 tackles and one sack.[4] In 2018, he converted to linebacker.[5] In a game against Louisville, he had a 27-yard pick six in a 77–16 victory.[6] In 15 games, Simmons had 97 tackles, 1.5 sacks and one interception.[7][8] He returned to Clemson in 2019 rather than enter the 2019 NFL draft.[9] Simmons received the Butkus Award as the nation's best linebacker for his performance that year.[10] After graduating in December 2019 with a degree in sports communication, Simmons announced that he would forgo his senior year by declaring for the 2020 NFL draft.[11][12] During his time at Clemson, Simmons was noted for his positional versatility, taking snaps at linebacker, defensive end, cornerback, and safety.[13][14]
Simmons participated in the 2020 NFL Combine, leading all linebackers with a 4.39-second 40-yard dash.[18] He was one of 58 players invited to the 2020 NFL Draft, which was held virtually due to social distancing regulations arising from the COVID-19 pandemic, where he was selected by the Arizona Cardinals with the eighth overall pick.[19][20]
Simmons entered the 2021 season as a starting inside linebacker. He started all 17 games, finishing third on the team with 105 tackles, 1.5 sacks, four forced fumbles, and seven passes defensed.[23][24]
In Week 7 against the New Orleans Saints, Simmons recorded five tackles and returned an interception 56 yards for his first NFL touchdown in the second quarter in the 42–34 win.[25] In the 2022 season, he finished with four sacks, 99 total tackles (68 solo), two interceptions, seven passes defended, two forced fumbles, and one fumble recovery in 17 games and 13 starts.[26]
On May 1, 2023, the Cardinals declined the fifth-year option of Simmons' contract, making him a free agent in the 2024 offseason.[27]
During a Week 11 game against the Washington Commanders, Simmons intercepted a pass off of Sam Howell and returned it for a touchdown, sealing the game and resulting in a victory for the Giants.[30] In the 2023 season, he finished with one sack, 50 total tackles (33 solo), one interception, three passes defended, one fumble recovery, and one forced fumble in 17 games and four starts.[31]
On April 5, 2024 the Giants re-signed Simmons to a 1 year, $2,000,000 deal.[32]
On October 6, 2024, in a game vs. the Seattle Seahawks, Simmons blocked a potential game-tying field goal from Jason Myers, which was returned for a touchdown by Bryce Ford-Wheaton, as the Giants won 29-20.
