He played college football for the USC Trojans, and was selected by the Cleveland Browns in the third round of the 2016 NFL draft.

[12] Kessler led USC to a 10–4 record, finishing the year 7–2 under interim head coaches Ed Orgeron and Clay Helton.

[13] Kessler was 22-for-30 for 345 yards with a career-best four touchdowns in the 2013 Las Vegas Bowl rout over Fresno State, and received Most Valuable Player (MVP) honors.

On August 30, 2014, Kessler threw for a career-high 394 yards and accounted for four total touchdowns against Fresno State, leading to his first of three designations as Pac-12 Offensive Player of the Week.

[16][17] On October 18, Kessler accounted for seven touchdowns against Colorado, the most ever by a USC quarterback, leading to his second designation as Offensive Player of the week.

[18][19] In the final game of the regular season, he threw six touchdowns against rival Notre Dame, the most touchdowns thrown by a single quarterback against Notre Dame in the 127-year history of the program, leading one Los Angeles Times writer to label him a potential 2015 Heisman Trophy candidate.

[22] Kessler started his final season with the Trojans off on a positive note with 240 yards and four touchdowns in a victory over Arkansas State.

[28] In the final game of his collegiate career, the Holiday Bowl against Wisconsin, he finished with 221 yards, one touchdown, and one interception in the 23–21 loss.

Kessler finished his debut completing 21-of-33 attempts for 244 passing yards as the Browns lost to the Miami Dolphins in overtime 30–24.

[38] On October 16, 2016, Kessler completed 26 of 41 pass attempts for a season-high 335 yards and two touchdowns during a 28–26 loss to the Tennessee Titans.

[40] In Week 11, Kessler made his eighth start of his rookie season against the Pittsburgh Steelers and finished the game with 7-of-14 attempts while throwing an interception.

In Week 16 against the San Diego Chargers, Kessler completed 2-of-3 passes for 11 yards after entering the game with 10 minutes left in the fourth quarter after Griffin suffered an injury.

[44] Kessler was inactive for the first six games of the 2017 season as the third-string quarterback behind Kevin Hogan and rookie DeShone Kizer.

Kessler was expected to compete with Nate Sudfeld and rookie Clayton Thorson for the backup job to Carson Wentz.