Michigan continued to win, rising to number two in the College Football Playoff rankings at 9–0 before falling on the road to Iowa on a last-second field goal.

The team was led by unanimous first-team All-American linebacker Jabrill Peppers, who was the Big Ten Defensive Player of the Year and a finalist for the Heisman Trophy, finishing in fifth.

Michigan suffered staff attrition when defensive coordinator D. J. Durkin left the program to become the head coach at Maryland.

[2] On January 7, 2016, it was officially announced that John Baxter would be leaving Michigan to become the Special Teams coach at USC.

He was replaced by Brian Smith, who most recently served as an assistant linebackers coach with the Philadelphia Eagles under Chip Kelly.

[7] Michigan also conducted several satellite camps—football camps meant to expose prospective student athletes to colleges who might otherwise not find and recruit them due to distance or other factors—in 22 states, Australia, and American Samoa following the NCAA's reversal of a ban enacted only months prior.

Michigan alumna Dana Jacobson hosted the event, while former Wolverine great Charles Woodson was also in attendance.

The radio announcers are Jim Brandstatter with play-by-play, Dan Dierdorf with color commentary, and Doug Karsch with sideline reports.

Thirty-three Wolverines made their collegiate debut, while seventeen true freshmen appeared in the game, setting a program record.

Michigan added 13 points in the second quarter via a 24-yard, and 36-yard field goal from Allen, and a 14-yard touchdown pass from Speight to Butt.

Michigan responded with a six-yard blocked punt touchdown return by Grant Perry, which reduced Colorado's lead to seven points.

[56] Following its game against Colorado, Michigan began its Big Ten portion of the schedule when it hosted the Penn State Nittany Lions.

Penn State opened the scoring in the fourth quarter via an eight-yard pass from Trace McSorley to Chris Godwin.

[74] Following its clash with Rutgers and its bye week, Michigan hosted the Illinois Fighting Illini for its homecoming game.

Amara Darboh extended his streak of consecutive games with a catch to 27 and now holds sole possession of the sixth spot among Michigan leaders in the category.

Michigan added 10 points in the third quarter via a 29-yard field goal from Kenny Allen, and a one-yard touchdown run from Smith.

This was the first game the Wolverine offense featured a 300-yard passer (Wilton Speight, 362), a 100-yard rusher (De'Veon Smith, 114) and a 100-yard receiver (Jehu Chesson, 112) since October 19, 2013, vs. Indiana.

Jake Butt became the program's all-time leader for receiving yards from a tight end (1,521), surpassing the previous record set by Jim Mandich (1,508).

Iowa responded with a Jaleel Johnson safety and a three-yard touchdown pass from C. J. Beathard to Akrum Wadley, which made the score 10–8 in favor of Michigan at half-time.

With two pass breakups against the Hoosiers, cornerback Jourdan Lewis upped his career total to 43 to tie Leon Hall (2003–06) for the most in Michigan history.

[94] Following its home finale against Indiana, Michigan faced its arch-rivals, the Ohio State Buckeyes, in the 113th meeting of "The Game".

Ohio State reduced Michigan's lead to three points via a one-yard touchdown run from Mike Weber, before Tyler Durbin recorded a 23-yard field goal as time expired in the fourth quarter to tie the game and force overtime.

In double overtime, Michigan scored via a 37-yard field goal from Allen, before Curtis Samuel recorded a 15-yard touchdown run to win the game, after J. T. Barrett was ruled to have converted a 4th down on the previous play.

Darboh has recorded a reception in 32 consecutive games, earning a share of the fourth spot among Michigan's all-time leaders in the category.

[97] The Big Ten fined Head Coach Jim Harbaugh and the school $10,000 for violating their sportsmanship policy after he was critical of the officiating crew at a post-game press conference.

Florida State extended its lead with a 42-yard field goal from Roberto Aguayo and a 92-yard touchdown pass from Deondre Francois to Nyqwan Murray.

Florida State's extra point was blocked by Chris Wormley, and Josh Metellus returned it the length of the field for a defensive conversion, making the score 33–32 in favor of the Seminoles.

Michigan took over possession at its 25-yard line following the kickoff but was unable to get anything going as a fourth-down pass was intercepted near midfield to seal the game.

Allen finished his career at 37-for-45, an 82.2-percent clip, just short of passing Bob Bergeron (29-of-35; 82.9 percent) as Michigan's all-time most accurate field goal kicker (minimum of 15 attempts).

Wide receiver Amara Darboh finished his career with at least one catch in 33 straight games, the fourth-longest streak in program history.