[2] He also played basketball for his high school, was on the honor roll, and a member of the Future Business Leaders of America.

[3] As a sophomore in 2012, Dupree started all 12 regular season games and recorded 91 tackles, 12.5 tackles-for-loss and 6.5 sacks.

[5][6] Dupree returned as a starter at defensive end his senior season in 2014 and was voted team captain for the Wildcats that year.

He also started all 12 games and recorded his first career interception which he returned for a game-winning touchdown in a 45–38 win against South Carolina.

[11] Coming out of college, Dupree was projected to be a first round draft pick by the majority of NFL analysts.

[12] Analysts and scouts gave him positive reviews for his freakish athleticism, explosive burst, large frame, outstanding power and strength, ability to play zone coverage, and character.

[20] He was the first University of Kentucky player taken in the first round since defensive tackle Dewayne Robertson went with the fourth overall pick to the New York Jets in the 2003 NFL draft.

Dupree made his professional regular season debut in the Steelers' regular-season opener against the New England Patriots and finished the 28–21 loss with two solo tackles and sacked Tom Brady.

He finished his rookie season with 26 combined tackles, four sacks, and a pass deflection while playing in all 16 regular-season games and five starts.

[25] Dupree was named the starting left outside linebacker ahead of Moats to begin the 2016 regular season.

[25] Head coach Mike Tomlin named Dupree the left outside linebacker to begin the season, opposite T. J.

[30] On September 17, 2017, he made his season-debut and collected two combined tackles, deflected a pass, and sacked Vikings quarterback Case Keenum during a 26–9 victory.

In Week 4, Dupree recorded four solo tackles and sacked Joe Flacco, as the Steelers defeated the Baltimore Ravens 26–9.

[35][36] In week 12 against the Cincinnati Bengals, Dupree recorded a strip sack on Ryan Finley and recovered the football in the 16–10 win.

[41] In week 12, against the Baltimore Ravens, Dupree tore his ACL and was placed on season-ending injured reserve the following day.

[43][44][45] Heading into training camp, Dupree was placed on the physically unable to perform (PUP) list on July 24, 2021.

[56] In the early hours of February 18, 2022, Dupree turned himself in to police after being cited for misdemeanor battery charges for an attack against an employee at a Nashville Walgreens after a game against the Miami Dolphins.