[4] Zappe was not heavily recruited and committed to play college football at Houston Baptist University, which was his only scholarship offer.

[10] Zappe committed to transfer to Western Kentucky University, following former Houston Baptist offensive coordinator Zach Kittley.

[15][16] During the 2021 regular season, Zappe led the Football Bowl Subdivision (FBS) passing for 5,545 yards and throwing for 56 touchdowns.

In the 2021 Boca Raton Bowl against the Appalachian State Mountaineers, he broke both records, finishing the season with 5,967 passing yards and 62 touchdowns.

[26] He made his starting debut the following week against the Detroit Lions, completing 17 of 21 passes for 188 yards, a touchdown, and an interception in the 29–0 shutout victory.

[27] After a Week 6 victory over the Cleveland Browns, during which he threw for 309 yards and two touchdowns, Zappe became the Super Bowl era's first rookie quarterback to win his first two starts and have a passer rating of at least 100 in each.

[34] After making several relief appearances throughout the season, Zappe was named the starter against the Los Angeles Chargers after struggles from Mac Jones.

He started the following game against the Pittsburgh Steelers on Thursday Night Football, leading the Patriots to a 21–18 upset win as he passed for 3 touchdowns in the first half.