In 2022, McCarthy led Michigan to an undefeated regular season, a Big Ten Conference championship and a berth in the 2022–23 College Football Playoff (CFP).

In 2023, McCarthy was named the Big Ten Quarterback of the Year after leading the Wolverines to a 15–0 record and a national championship, the program's first since 1997.

McCarthy finished his college career with a 27–1 record (.964) as a starting quarterback, the highest winning percentage in NCAA Division I Football Bowl Subdivision (FBS) history.

[3] In his lone season at IMG, he led his team to an 8–0 record and a consensus high school football national championship.

[5] At age 16, McCarthy said Ryan Day "lied to my face" by telling him in March that Ohio State would not take a quarterback in the 2021 recruiting class until the end of the summer, but then accepted a commitment from Kyle McCord in April.

"[10] In eighth grade, he received a scholarship offer to play football at Iowa State from head coach Matt Campbell.

[21] In the final game of the regular season against Ohio State, McCarthy helped Michigan defeat the Buckeyes to advance to the 2021 Big Ten Championship.

[29] In his postgame press conference, Harbaugh announced that McCarthy would start against UConn in week 3 and added, "He's the starter moving forward on merit.

[41] On September 2, 2023, in the season opener against East Carolina, McCarthy recorded his best career passing game at home, throwing for 280 yards and three touchdowns.

On January 1, 2024, in a 27–20 overtime win against Alabama in the Rose Bowl, he completed 17 of 27 passes for 221 yards and three touchdowns to three different receivers, Roman Wilson, Blake Corum and Tyler Morris.

[51][52] McCarthy finished his career at Michigan with a 27–1 record (.964) as the starting quarterback, the best winning percentage in NCAA Division I Football Bowl Subdivision (FBS) history (1978–present), the third-best winning percentage in major college football history, and the best by any college quarterback since 1971.

[53][54] In each of his three years at Michigan, the Wolverines beat Ohio State, won the Big Ten title, and advanced to the CFP semifinal.

[64] Following the preseason opener against the Las Vegas Raiders, in which he threw two touchdowns, he reported soreness in practice and was found to have fully torn his meniscus in his right knee.

[65][66][67] McCarthy underwent surgery to repair it and was placed on injured reserve, becoming the first quarterback selected in the first round to miss his entire rookie season due to injury.

[2][70][71][72] McCarthy is engaged to high school sweetheart Katya Kuropas, who he proposed to just weeks after winning the national title.