Quarterback Marcus Mariota didn't let that happen, leading the Ducks on six consecutive scoring drives to lift Oregon to a 48-14 win over the Cowboys.
Mariota became the fourth Oregon quarterback to pass for more than 7,000 yards. The Ducks junior completed 19 of 23 passes with two touchdowns. Mariota also rushed five times for 71 yards, including touchdown runs of 15 and 19 yards.
Mariota has thrown a school-record 71 touchdowns, with at least one TD thrown in all 29 games he's appeared in.
Oregon (3-0) had a rare scoreless first quarter, and found itself trailing 7-0 heading into the second quarter.
"We were a little sluggish at the beginning in every phase. Whether it's the early game or whatever, we're in the business of fighting human nature. It's impossible to ignore to some degree," Oregon coach Mark Helfrich said. "Our guys did a decent job of shaking the hangover."
Mariota paced Oregon by leading the Ducks on four second-quarter scoring drives. Mariota ran for two scores and threw a 16-yard touchdown pass to Devon Allen that gave Oregon a 27-7 halftime lead.
"I don't know if anyone in this room has a vote for the Heisman Trophy, but I encourage you to take a look at your ballot there for [this] quarterback. He's a tremendous player and I thought he played extremely well," Wyoming coach Craig Bohl said.
Highlighting Mariota's performance was a second-quarter touchdown where the Honolulu junior gave Ducks fans a thrill and scare at the same time.
Scrambling to avoid a pass rush, Mariota ran 19 yards for a touchdown, finishing the play by diving head first over Wyoming tacklers to reach the pylon.
Mariota bounced off the ground and ran to the sideline.
"I hope he never does that ever again. Pretty sure all our coaches don't want to see him do that again," said Oregon receiver Keanon Lowe, blocking for Mariota on the play. "I'd rather see him run out of bounds at the 2. That being said, it was an awesome play."
Helfrich said that play was Mariota being Mariota.
"He can't sit there and think, don't do this, don't do that. The way he plays, that's one of his biggest strengths," Helfrich said.
Helfrich wasn't entirely thrilled with seeing his Heisman Trophy hopeful going airborne, however.
"He told me on the sideline to never do that again. I'll take that as a warning," Mariota said.
Oregon safety Erick Dargan had two interceptions, both in the first half.
Wyoming, a 43-point underdog to Oregon, had some moments, but couldn't stop the Ducks' offense after the first quarter.
The Cowboys (2-1) had 439 yards, including 282 during the first half. But Wyoming allowed Oregon to score on six consecutive possessions, three set up by Cowboy turnovers.
The loss ended a personal 26-game winning streak for Bohl, the first-year Cowboys coach who won three consecutive FCS national titles at North Dakota State (2011-13).
"We knew it was going to be an uphill challenge and we were going to have to play error-free. We certainly didn't do that," Bohl said. "I'm not saying everything was beautiful out there, but by and large, I felt like our guys stayed in it, kept on trucking, kept on believing."
Wyoming stunned Oregon early, stopping the Ducks' first drive on fourth down at the Cowboys 2. Wyoming rewarded its defense by driving 98 yards for the game's first score, an 18-yard touchdown pass from Kirkegaard to Tanner Gentry.
Oregon right tackle Jake Fisher, a three-year starter, left the game during the Ducks' opening drive with a leg injury.
The Ducks ended Wyoming's upset hopes with a 27-point second quarter.
"It's good to go through a little adversity. You have to fight through some things. It wasn't a factor that we weren't moving the ball. For us, it's punching it in and finishing," Mariota said.
Oregon tied the game at 7-7 just five seconds into the second quarter on a 15-yard touchdown scramble by Mariota. The Ducks took a 13-7 lead four minutes later when Marshall romped 30 yards for a score.
Two interceptions by Dargan set up Oregon's final two scores of the second quarter.
Allen caught a 16-yard touchdown pass from Mariota with 1:34 remaining in the second quarter, giving Oregon a 27-7 lead that it took into halftime.
The Ducks continued their offensive roll into the third quarter, when Oregon scored on its first two possessions to take a 41-7 lead. Mariota left the game after throwing a 5-yard touchdown pass to Johnathan Loyd with 9:59 remaining in the third.
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