He played college football for the Florida Gators and was selected third overall by the Jacksonville Jaguars in the 2015 NFL draft.

Fowler attended Lakewood High School in St. Petersburg, Florida, where he was a two-sport star in football and track.

Fowler was named an honorable mention to the Sports Illustrated All-American football team following his senior season, and was selected to the 2012 Under Armour All-America Game.

[5] In his final game, the 2015 Birmingham Bowl vs East Carolina, he recorded three sacks helping the Gators to the 28–20 victory.

[15] Fowler ended his first official season playing in all 16 games with one start, recording 32 tackles, 4 sacks, and five passes defensed.

Late in the third quarter, Fowler forced a fumble off of quarterback Deshaun Watson, which was recovered by teammate Yannick Ngakoue.

In the playoffs, Fowler recorded five tackles, two sacks, and a pass deflection before the Jaguars were defeated 24–20 by the New England Patriots in the AFC Championship Game.

In the playoffs, the Rams defeated the Dallas Cowboys in the Divisional Round and Fowler recorded 2 tackles and a sack.

In the NFC Championship Game against the New Orleans Saints, Fowler recorded 5 tackles and 0.5 sacks in a 26–23 overtime victory to advance to Super Bowl LIII and Fowler made a huge play in overtime when he hit Drew Brees to set up an interception by John Johnson III.

[22] In the season-opener against the Carolina Panthers, Fowler sacked Cam Newton twice as the Rams won on the road by a score of 30–27.

[24] Three weeks later against the Pittsburgh Steelers, Fowler recovered a fumbled snap by center Maurkice Pouncey and returned it for a 26 yard touchdown in the 17–12 road loss.

He appeared in 14 games with six starts, registering 36 tackles (6 for loss), 4.5 sacks (led the team), 8 quarterback pressures and a career-best three forced fumbles.

He appeared in all 17 games as a pass rushing specialist at defensive end, collecting 20 tackles (3 for loss), 6 sacks and 29 quarterback pressures.

[34] He remained as a backup rotational player at defensive end, appearing in all 17 games, posting 13 tackles (5 for loss), 4 sacks and 7 quarterback pressures.

[38] His younger brother, Donterio Fowler, was arrested in July 2021 in connection to a 2016 murder of a Florida International University student.