[8][9] Consensus All-American running back Kenneth Walker III,[10] offensive lineman Kevin Jarvis,[11] and wide receiver Jalen Nailor declared for the NFL draft.

[16] On January 16, it was announced that defensive line coach Ron Burton was leaving the school after eight years with the Spartans.

[17] On February 8, the school named Georgia Tech assistant Marco Coleman the new defensive line coach.

[19] MSU captain and leading tackler, safety Xavier Henderson, also announced he would return for the 2022 season.

The Broncos moved into MSU territory on their next possession before stalling at the Spartans 10 yard line and settling for a field goal to give WMU the early 3–0 lead.

MSU answered quickly, moving into Bronco territory in four plays before freshman wide receiver Germie Bernard caught a 44-yard touchdown pass from Payton Thorne to give the Spartans the 7–3 lead.

Following another punt by Western Michigan, the Spartans scored on a two-play drive that ended with Thorne's third touchdown pass of the season, this one to Keon Coleman.

Following a punt by the Spartans, the Broncos again moved into MSU territory, but a fumble by WMU running back Sean Tyler was recovered by Simeon Barrow to again end the drive.

Following a WMU punt to start the third quarter, the Spartans moved to midfield before running Jalen Berger fumbled the ball and the Broncos recovered to end the drive.

Trailing 28–12, WMU went for it on fourth down with under five minutes remaining, but were unsuccessful, setting the Spartans up at the Bronco 43.

On the first play of the drive, Thorne threw his fourth touchdown on the day, this to Tre Mosley, to push MSU's lead to 35–13 with just over four minutes left in the game.

[30] The Spartans were without top defenders linebacker Darius Snow, who was injured in the prior game and will miss the rest of the season, and safety Xavier Henderson.

Jalen Berger gouged the Zips defense and Payton Thorne hit Jayden Reed to put the ball at the Akron seven.

Jarek Broussard took over at running back and moved the ball to the on and then into the end zone to give MSU the early 7–0 lead.

The teams exchanged punts on their next possessions before the Zips turned it over again on forced fumble by Jacoby Windmon.

As time ran out, Jack Stone kicked his first field goal from 43 yards to give MSU the 24–0 halftime lead.

With the Spartans starting the half with the ball, Thorne was intercepted on the first play from scrimmage on a deep pass that resulted with Akron taking over at their own 30.

Two plays later, Haladay sacked Zips' backup quarterback Jeff Undercuffer and forced a fumble that was recovered by MSU at the Akron 20.

On the second play of the drive, Kim threw a 16-yard touchdown pass to Tre Mosely to give MSU a 31–0 lead.

Washington immediately took control of the game driving quickly into Spartan territory and scored an eight-yard touchdown pass by Penix to give the Huskies the early 7–0 lead.

However, on the first play from scrimmage, Jarek Broussard slipped coming out of the backfield and did not make it out of the end zone resulting in a safety and a 9–0 Washington lead.

The ensuing free kick went out of bounds and the Huskies quickly scored again to move the lead 16–0 early in the second quarter.

The Spartans embarked on a 15-play, 75-yard drive including two fourth down conversions and capped off by Payton Thorne's touchdown pass to Keon Coleman.

The MSU defense was exploited again by Penix on the ensuing possession and he threw his fourth touchdown pass of the game as the lead moved to 36–14 with just under 11 minutes left in the third quarter.

Thorne threw his third touchdown pass of the game, his second to Keon Coleman, but the two-point conversion failed.

Following a Washington punt, the Spartans were able to move to midfield, but turned the ball over on downs with less than three minutes left in the game.

Once again, the Spartan defense was decimated by the opponent as the Gophers scored on their first possession, easily moving down the field to take a 7–0 lead.

Following a three-and-out for MSU, the Gophers embarked on a nine-play drive as they again moved downfield easily and pushed the lead to 14–0.

Looking to get back into the game to start the third quarter, the Spartans moved into Gopher territory before Thorne fumbled the ball at the Minnesota six, ending the drive.

Following yet another punt by MSU, the Gophers wen on a 15 play, 76-yard drive that took over 10 minutes before settling for a field goal to push the lead to 34–0 with 1:48 left in the game.