The Wolverines responded well to the challenge, going ahead on De'Veon Smith's 42-yard run early in the third quarter and pulling away to beat Colorado 45-28 on Saturday.
"In the first two games, we were never really punched in the face," tight end Jake Butt said after making seven receptions for 87 yards. "It wasn't going to be a fairy tale the whole season."
Michigan (3-0) had beaten Hawaii and Central Florida by a combined score of 114-17.
The Wolverines scored 17 straight points after falling behind 21-7 late in the first quarter. Michigan scored the last 21 points of the game, capped by Jabrill Peppers' 54-yard punt return early in the fourth.
"The best way to deal with adversity is to not have it," said Wilton Speight, who was 16 of 30 for 229 yards and a TD. "We were hoping to not have any adversity. Is that realistic? Maybe not. But when you look at yourself as a good team, maybe a great team, you want to avoid it as much as possible.
"We really couldn't do anything in the beginning, but we saw adversity in the eye and came back at it."
The Buffaloes (2-1) got to midfield on the final possession, but they were more than a Hail Mary away by the end of the matchup, which rekindled memories of Kordell Stewart's 64-yard pass to Michael Westbrook in 1994 in the same stadium. Both Stewart and Westbrook attended Saturday's game.
It didn't help that Sefo Liufau was hurt after throwing his third TD pass, a 70-yarder to Shay Fields that put Colorado up 28-24 just after halftime.
Liufau, who was shaken up in the first half, grabbed his right ankle after Ryan Glasgow hit him on the go-ahead score. He limped through Colorado's next series before being replaced by freshman Steven Montez.
The senior quarterback said it was "devastating," to be relegated to watching the rest of the game.
"It's a little over-dramatic, I think, but I can't really find another word right now," he said.
Punting was also problem for the Buffaloes.
Grant Perry returned a blocked punt for a 6-yard score when Michigan was trailing 14-0 late in the first quarter. Colorado punter Alex Kinney booted the ball into a teammate's back in the second quarter, setting up the Wolverines for Jehu Chesson's 17-yard run that pulled them within a TD.
"It was a big part of the game of us not coming out on top," Buffaloes coach Mike MacIntyre said.
Colorado: The Buffaloes look as if they should have enough talent to win more than four games, the most they've won in MacIntyre's previous three years at the school.
"We have a good football team," he said. "There were a couple of things that happened out there that changed the momentum a little bit, but our guys kept battling hard.
Colorado has to hope Liufau is not injured seriously again.
"I just couldn't plant, and throw with much velocity," Liufau said. "It was better for me to come out."
Michigan: The Wolverines are giving up big plays, allowing Colorado to go nearly three-fourths of the field on one play a week after letting Central Florida run for 80-plus yards on two runs.
"We definitely have to get the big plays corrected," Peppers acknowledged.
Speight struggled for the first time, barely completing half of his passes and nearly getting picked off several times.
"It wasn't as clean as a quarterback would have liked it to be," coach Jim Harbaugh said.
The Wolverines will likely move up a spot in The Associated Press college football poll because No. 2 Florida State lost 63-20 to Louisville.
CATCH WITH THE CAPTAIN
Tom Brady was Michigan's honorary captain, accepting the invitation to come back to Michigan while he is suspended for four games from playing for the New England Patriots. Harbaugh, another former Wolverines quarterback, played catch with Brady during pregame warmups.
"He can whip it," Harbaugh said with a grin. "He can throw it well. I wish I wouldn't have given him the wind."
Colorado: The Buffaloes, who have only one Pac-12 win in two of MacIntyre's three years and went 0-9 in 2014, open the conference season with a tough test at Oregon.
Michigan: The Wolverines, whose last Big Ten title was in 2004, will play their fourth of five straight games at home against Penn State in their conference opener.