Mariota found sophomore Keanon Lowe with a 21-yard scoring pass before Avery Patterson scored on a 43-yard interception return. It was Patterson's second straight game with an interception return for a touchdown.
Sankey, who had also run for 100 yards in each of Washington's previous two games, had a 1-yard touchdown dive for the Huskies to make it 21-7 early in the second quarter.
The Ducks answered with Mariota's 10-yard TD pass to Lyerla. A short time later, a running Mariota hit Josh Huff with a 34-yard catch-and-run.
Rob Beard, who missed a 41-yard field goal attempt in the first half, made a 28-yarder early in the second to make it 38-7.
Sankey ran for a hard-fought 6-yard touchdown before the end of the third quarter.
Lyerla opened the fourth with a 13-yard touchdown pass from Mariota, and a short time later Byron Marshall ran for a score to make it 52-14.
Erich Wilson had a 1-yard TD run for Washington with 32 seconds left in the game.
"I don't think the final score is indicative of their football team as compared to ours and that part's really frustrating to me," Sarkisian said.
Washington popped into the rankings last week after a 17-13 victory over then-No. 8 Stanford.
The Ducks were the Huskies' third top-10 opponent this season. Washington also fell 41-3 to then-No. 3 LSU.
They struggled as much against the Ducks, who went into the game averaging more than 52 points a game and 550 yards in total offense.
Last season, Oregon defeated Washington 34-17 in the final game played at the old Husky Stadium before an extensive renovation that is set to be completed for the 2013 season.