Mariota went 24-for-31 with 366 yards for the Ducks (6-0, 3-0 Pac-12), who have scored 147 points in their three conference games. He also had 13 carries for 88 yards.
Byron Marshall had 19 carries for 106 yards and two scores, while Bralon Addison had two touchdown catches amongst his eight receptions for 157 yards.
"Obviously, Marcus -- you can't say enough about how he played, but at the same time it is an 11-man offense," said Oregon head coach Mark Helfrich. "It was just a total team victory."
Keith Price was 19-for-32 with 182 yards, one touchdown and one interception for the Huskies (4-2, 1-2), who have dropped their past two games after beating Arizona to open conference play. Bishop Sankey had 28 carries for 167 yards and two touchdowns.
"They're a good football team," said Washington head coach Steve Sarkisian. "Their ranking is deservedly so. I thought our kids played hard, I thought we fought, I thought we showed a lot of resolve during the third quarter and battling back into the ball game. We just unfortunately had a hard time containing Marcus Mariota. He threw the ball extremely well and when we covered him, he ran."
Washington started the second half with the ball and trailed by 14, but the fourth play of the drive saw Sankey take a handoff around the left side and race into the end zone untouched on a 60-yard score.
Oregon, though, quickly answered as Mariota went deep over the middle on the third play and found Josh Huff in-stride for a 65-yard score and a 28-14 lead with 12:36 left in the third.
The next possession for Washington nearly ended badly as a pass appeared to be intercepted, but it was overturned and the team eventually got a 30-yard field goal from Travis Coons to make it a 28-17 game with 7:25 left in the third.
The Ducks came right back with a field goal of their own as Alejandro Maldonado's 34-yard boot capped an 11-play, 66-yard drive for a 31-17 advantage.
Washington responded with a 25-yard touchdown from Sankey that saw him take a handoff to the inside and break through the right side to make it a 31-24 game with just 26 seconds left in the third.
Mariota, though, took the ball 35 yards on the next play down to the Washington 36, and later took the ball into the end zone from five yards out for a 38-24 lead just over a minute into the fourth.
After holding the Huskies, the Ducks put the game away as Addison caught a 3- yard score for a 45-24 advantage with 7:37 left.
Oregon was held on a 4th-and-5 attempt at the Washington 31 on the first drive of the game, but then held the Huskies to a three-and-out before getting the ball back.
Starting at the 23, four straight rush plays moved the ball 23 yards and a 43- yard catch from Addison moved the ball to the Washington 9. Following an overturned touchdown call on 3rd-and-goal at the 1, Marshall was able to bull the ball in from a foot out and that score was upheld to give the Ducks a 7-0 lead with 6:22 to play in the first.
Washington came right back to tie the game and got into scoring position thanks to catches of 13 yards from Kevin Smith followed by a 28-yard grab from Jaydon Mickens. Three plays later, Austin Seferian-Jenkins made a leaping 8- yard grab in the back of the end zone for a 7-7 game with 3:52 to play in the first quarter.
The score stayed that way until 8:41 showing on the clock in the second quarter when Addison made a leaning catch along the right side of the end zone from four yards out to give Oregon a 14-7 lead. The eight-play, 69-yard drive was highlighted by a 38-yard catch from Addison on the first snap of the march.
A three-and-out from Washington saw Oregon get the ball back at its 37 a minute later. An 18-yard catch from Pharaoh Brown moved the ball across midfield and a 20-yard catch from Keanon Lowe moved the ball to the 15. On the next play, Marshall took a handoff into the end zone for a 21-7 lead with 4:55 to play in the half.
Oregon totaled 631 yards and controlled the ball for almost 34 minutes, while Washington had 376 yards ... Huff finished with six catches for 107 yards ... Oregon has won 10 straight against Washington, but the Huskies still lead the series, 58-43-5 ... Oregon hosts Washington State next week ... Washington plays at Arizona State next week.
10/12 23:24:54 ET