Mariota kicked things off with a 57-yard scoring dash on the first series of the game for the Ducks, who wore pink helmets, cleats and socks for Breast Cancer Awareness Month. Byron Marshall ran for 192 yards and three touchdowns for Oregon (7-0, 4-0 Pac-12).
Halliday completed 58 of 89 passes for 557 yards and four touchdowns for the Cougars (4-4, 2-3). His attempts broke the FBS-level record of 83 set by Drew Brees of Purdue on Oct. 10, 1998. His total attempts and completions also broke the Pac-12 records set by Arizona's Matt Scott last season, and his total yards set a Washington State record.
But Halliday also threw four interceptions, including one that was returned 51 yards for a touchdown by Terrance Mitchell early in the fourth quarter. The junior leads the nation with 18 interceptions.
Mariota had his first two turnovers of the season, two fumbles that led to first-half Washington State touchdowns, and the Cougars came within 27-21 in the second quarter.
The Ducks cleaned up the mistakes in the second half and pulled away, racking up 719 yards in total offense. Freshman Thomas Tyner ran for 99 yards and two touchdowns.
The Ducks were coming off a 45-24 victory over Washington in Seattle last weekend. After Stanford's upset loss to Utah last week, undefeated Oregon is alone in first place in the Pac-12 North.
The Cougars were coming off a 52-24 loss to Oregon State in Pullman last weekend. The Beavers outscored Washington State 28-0 in the fourth quarter and Halliday threw three interceptions
Oregon remained without dynamic running back De'Anthony Thomas, who was in pads and practiced before the game but didn't play for the third straight game. Thomas, who has run for 338 yards and six touchdowns, has been out since his slipped on the rain-soaked turf at Autzen on the opening kickoff against Cal.
After Mariota's opening touchdown, Marshall plowed across the line for a 1-yard touchdown midway through the first to up Oregon's lead to 13-0. Halliday found Dom Williams in the corner of the end zone with an 11-yard scoring pass, but Marshall answered with a 26-yard scoring run to make it 20-7.
Tyner made an acrobatic catch to get to the Washington State 1, then powered into the end zone for the touchdown early in the second quarter.
Mariota was sacked and his fumble was recovered by Washington State, leading to Halliday's 22-yard pass to River Cracraft for the freshman receiver's first touchdown.
He was sacked and fumbled again on the next series and Xavier Cooper scooped up the ball and ran it in to narrow the score to 27-21 with 5:35 left before halftime.
Tyner scored on a 66-yard run for the Ducks before Andrew Furney kicked a 49-yard field goal for the Cougars as time ran out to make it 34-24.
Mariota found Keanon Lowe with a 10-yard scoring pass and Marshall scored on a 30-yard run in the third quarter before Mitchell's pick six early in the fourth.
Halliday threw an 8-yard touchdown pass to Gabe Marks with 3:48 left and added a 3-yard scoring toss to Bobby Ratliff with 11 seconds to go for the final margin.
Halliday's passing yards surpassed Alex Brink's Washington State record of 531 against Oregon State in 2005.
The Ducks extended their winning streak over the Cougars to seven straight.
Washington State defeated a ranked opponent earlier this season when they beat then-No. 25 USC 10-7, although it was before the Trojans fired head coach Lane Kiffin. The Cougars have not defeated a team in the top five since 2003, when they downed No. 5 Texas 28-20 in the Holiday Bowl.
Oregon planned to auction a number of the pink helmets off after the game to raise money for Kay Yow Cancer Fund, named after the North Carolina State women's basketball coach who died of breast cancer in 2009.