[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.

[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] Despite playing only five snaps in Week 7 against the Seattle Seahawks on Sunday Night Football, Simmons recorded his first career interception off Russell Wilson with a minute left in overtime, helping the Cardinals win 37–34.

[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.