Book sat behind Wimbush throughout the 2017 season, but he started for an injured Wimbush against North Carolina, propelling the Irish to a 33-10 victory over the Tar Heels in his first collegiate start on October 7, 2017. During the 2018 Citrus Bowl, Book came off the bench and led the Irish to a 21–17 victory over LSU.
Redshirt sophomore season (2018)
After a pair of slim home victories over unranked opponents Ball State and Vanderbilt in 2018, Book was chosen as the starter over Wimbush for a road game against Wake Forest. The result was a 56–27 Notre Dame victory, with Book throwing for 325 yards and two touchdowns, and running for three more. Against #7 Stanford the next week, Book threw for 278 yards and four touchdowns in a 38-17 rout of the Cardinal. The Irish continued to move up the rankings under Book, and in week 10, Book threw for two touchdown passes and ran 23 yards for a score in the closing minutes to lead No. 3 Notre Dame to a close 31-21 victory over Northwestern. Book helped the Irish to finish the regular season 12-0 and earn its first College Football Playoff berth, although the Irish were defeated by the eventual national championClemson in the 2018 Cotton Bowl Classic, 30-3.
Redshirt junior season (2019)
On September 14, 2019, Book threw for 360 yards and five touchdowns. He also had one rushing touchdown in a 66-14 win over New Mexico. He contributed to the most points scored in a home opener at Notre Dame since 1932. On October 5, 2019, Book threw five touchdowns in the first half against Bowling Green State University, becoming the first player in Notre Dame history to have five scores in one half. On November 9, 2019, Book threw four touchdown passes in a win against Duke University. Giving him 44 touchdown passes currently on the season. Making him sixth all-time at Notre Dame for touchdown passes in a career. On November 16, 2019, Book threw for 284 yards and five touchdowns against Navy Midshipmen football, making him the first Notre Dame quarterback in history to have five touchdown passes in three games for one season. On December 29, 2019, Book threw for 247 yards and a touchdown against the Iowa State Cyclones. This was Book’s second Bowl victory as Notre Dame beat the Cyclones in The Camping World Bowl.
Redshirt senior season (2020)
On December 29, 2019, Book announced via Instagram that he would be returning to Notre Dame for a fifth season as a redshirt senior.