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The second-ranked Ducks were flying high after a nonconference victory over then-No. 7 Michigan State earlier this season, but Washington State and the start of Pac-12 play brought Oregon back to reality.
No one said the march toward college football's first playoff was going to be easy.
The Cougars and their Air Raid offense under coach Mike Leach pressured the Ducks (4-0, 1-0) throughout, and pulled even at 31 in the final quarter.
That's when Marcus Mariota took over, leading the Ducks on a 79-yard drive that was capped by a 6-yard touchdown pass to Keanon Lowe with 5:33 left for the final margin.
"We faced a ton of adversity, some self-inflicted, some not," Oregon coach Mark Helfrich said. "I thought our guys did a great job of just seeing it through."
Oregon remained at No. 2 in the AP Top 25 Sunday behind Florida State, which escaped 23-17 in overtime against Clemson on Saturday night.
Mariota was once again the standout for the Ducks.
The junior quarterback raised the stakes in the Heisman Trophy race by throwing for 329 yards and five touchdowns. He completed 21 of 25 passes without an interception and also rushed for 58 yards despite being sacked seven times — the most he's ever had in a game in his career.
Yep, that was four incompletions.
"Ridiculous," Helfrich said. "That's a joke. That guy is special and he did a great job, too, of taking some of the blame and the heat off the o-line and led them through it and did a great job rallying the defense in the second half, as well."
It was Mariota's 30th straight game with at least one touchdown pass — that's every game of his Oregon career — and his seventh game with four or more touchdown passes.
Lowe and speedster Devon Allen each had two touchdown catches for Oregon, which has an off week before hosting Arizona in a Thursday night game.
Mariota's Washington State counterpart, Connor Halliday, threw for 436 yards and four touchdowns, completing 43 of 63 passes, for Washington State (1-3, 0-1). The Cougars, who boast the nation's top passing attack, came into the game as 24-point underdogs but kept it close.
Oregon outscored the Cougars 17-10 in the second half to take the lead. After Mariota's pass to Lowe, the Cougars answered with a drive that stalled on the Oregon 35 and turned the ball over on downs.
The off-week is coming at a good time for the Ducks, who are hurting — especially on the offensive line. The Ducks don't talk about injuries as a policy, but senior Jake Fisher and junior Andre Yruretagoyena weren't available Saturday night. The Ducks started true freshman Tyrell Crosby at left tackle, and Matt Pierson made his first start at right tackle.
The Ducks will need to be rested for the Wildcats.
Last season, Mariota was nursing a knee injury when the then-No. 5 Ducks went to Tucson and lost 42-16. It was Oregon's second loss of the season, and it would effectively drop them out of a shot at a fifth-straight BCS bowl bid.
Associated Press Writer Nicholas K. Geranios in Pullman, Washington, contributed to this report.