He played college football for the Clemson Tigers and was selected by the Jaguars in the first round of the 2021 NFL draft.

[14] Etienne started his junior year at Clemson with a career-high 205 yards and three touchdowns in the first game of the season.

Despite projections that Etienne would enter the 2020 NFL draft, he announced on January 17, 2020, that he would return to Clemson for his senior year.

[20] On October 31, 2020, in a 34–28 win over Boston College, Etienne finished with two touchdowns and a career-high 264 all-purpose yards.

[21] With the performance, he scored a touchdown in 42 games, breaking Donnel Pumphrey's record for most in FBS history.

[30] During the Jaguars second preseason game against the New Orleans Saints, Etienne suffered a Lisfranc injury and was subsequently ruled out indefinitely.

[31][32] It was later revealed that Etienne had suffered a significant tear in the lisfranc zone of his foot, which required surgery, and prematurely ended his 2021 season.

[34] Etienne made his professional debut in the Jaguars' 2022 season opener against the Washington Commanders and had four carries for 47 rushing yards.

[35] Etienne recorded his first career touchdown in Week 7 against the New York Giants, adding 14 carries for 114 yards and 1 lost fumble in the 23–17 loss.

[42] On the Jaguars' final drive, Etienne had a 25-yard run on fourth down to set up the game-winning field goal attempt.

[43] During Week 5 against the Buffalo Bills at Tottenham Hotspur Stadium, Etienne finished with 136 rushing yards and two touchdowns as the Jaguars won 25–20.