[1] He played college football at Ohio State, and was selected by the Colts in the second round of the 2018 NFL draft.

[6] His redshirt freshman year at Ohio State, Lewis appeared in every game whether on defense or playing a small role on special teams.

[2] For his sophomore season, Lewis broke into the regular rotation and led the team in quarterback sacks with eight and finished second to teammate Joey Bosa in tackles for loss with fourteen.

[7][8] Lewis continued his award-winning ways in 2016, as he racked up 7.5 sacks, sealed a win against Wisconsin, was named a captain, and won multiple accolades while developing into a leader off the field.

[17][18] On January 27, 2018, Lewis recorded four combined tackles and a sack as part of Denver Broncos' head coach Vance Joseph's North team that lost 45–16 to the South.

[20][21] On March 22, 2018, Lewis participated at Ohio State's pro day and performed the majority of combine drills, but chose to skip the vertical jump.

At the conclusion of the pre-draft process, Lewis was projected to be a third or fourth round pick by the majority of NFL draft experts and scouts.

[36] He played in all 17 games in 2023, recording 25 tackles and four sacks;[37] he was also the team's 2023 recipient of the Ed Block Courage Award.