He played college football for the Notre Dame Fighting Irish and was selected by the Cleveland Browns in the second round of the 2017 NFL draft.

Kizer served as the Browns' starter during his rookie season, but his tenure lasted only one year after going winless and leading the league in interceptions.

[5] On June 11, 2013, Kizer announced his commitment to play college football at the University of Notre Dame for the Fighting Irish.

[6] Sources: Kizer redshirted his first year at Notre Dame in 2014 behind quarterbacks Everett Golson and Malik Zaire.

[8] During the second game of the season against Virginia, Kizer replaced an injured Zaire and helped lead Notre Dame to a victory.

With 12 seconds left, Kizer completed a 39-yard touchdown pass to wide receiver Will Fuller to give Notre Dame the lead.

[13] On New Year's Day, the Fighting Irish closed out their 2015 season with a 44–28 loss to Ohio State in the Fiesta Bowl.

Kizer also participated at Notre Dame's Pro Day and only ran positional drills in front of team scouts and representatives, including San Francisco 49ers general manager John Lynch and Pittsburgh Steelers offensive coordinator Todd Haley.

During a Week 5 17–14 loss to the New York Jets, Kizer was benched in favor of Kevin Hogan to begin the third quarter after throwing for 87 yards and an interception in the first half.

[40] During a Week 7 12–9 overtime loss to the Tennessee Titans, Kizer threw for 114 yards and two interceptions before being benched in favor of Cody Kessler in the third quarter.

[44] In the regular-season finale against the Steelers, Kizer finished with a season-high 314 passing yards, two touchdowns, and an interception as the Browns lost on the road by a score of 24–28.

[48][49] On March 14, 2018, Kizer was traded to the Packers in exchange for Damarious Randall and a swap of both fourth and fifth-round draft picks.

[50] During the season-opener against the Chicago Bears, Kizer played in place of an injured Aaron Rodgers in the first and second quarters, throwing for 55 yards and an interception, which was returned for a touchdown, while also losing a fumble after being strip-sacked.

[51] In the regular-season finale against the Detroit Lions, Kizer played in relief of Rodgers, who had suffered a concussion, and threw for 132 yards and an interception as the Packers were shut-out by a score of 31–0.