Oregon State (5-1, 3-0 Pac-12) won its fifth game in a row since a shocking opening loss to FCS Eastern Washington.
The home loss dealt a blow to Washington State's (4-3, 2-2) hopes of reaching a bowl for the first time since 2003.
Washington State led 24-17 late in the third quarter when the Beavers erupted for three quick touchdowns to take control of the game.
Mannion, the Pac-12 passing yardage leader, completed 34 of 51 passes and was intercepted once. Brandin Cooks caught 11 passes for 137 yards and two touchdowns, and ran for another. Richard Mullaney caught five passes for 122 yards.
Washington State quarterback Connor Halliday completed 26 of 49 passes for 248 yards as the Beavers were able to shut down WSU's potent pass attack. He was intercepted three times.
Washington State took the opening kick and drove to the Oregon State 9, but had to settle for an Andrew Furney field goal.
Oregon State's Trevor Romaine kicked a 20-yard field goal to tie the score at 3 at the end of the first quarter.
On the ensuing series, Halliday passed the Cougars to the Oregon State 3, where Marcus Mason ran it in for a 10-3 lead.
The Beavers replied with a 75-yard drive, with Mannion throwing a 7-yard touchdown pass to Connor Hamlett that tied the game at 10.
After a penalty-filled drive that forced WSU to punt, Oregon State took over on its 27 and raced down the field on the strength of a 46-yard pass from Mannion to Mullaney. But Mannion threw an interception to Anthony Carpenter in the end zone to kill the drive. Then Washington State fumbled on its first play and Oregon State took over on the WSU 36. Storm Woods scored on a 3-yard run to give Oregon State a 17-10 lead that stood up at halftime.
Mannion completed 18 of 29 passes for 253 yards in the first half.
A 26-yard punt return by Leon Brooks gave Washington State the ball on OSU's 41 on its first possession of the second half, and the Cougars drove to the 1. Jeremiah Laufasa plunged over for a touchdown to tie the score at 17.
On their next possession, Washington State went 80 yards in 10 plays, capped by a 4-yard pass on 4th-and-goal from Halliday to Vince Mayle in the end zone for a 24-17 lead with 4:50 left in the third. The touchdown was set up by a 40-yard reception by Mayle.
But Oregon State scored three times in less than three minutes.
First was an 82-yard drive that ended on a 7-yard touchdown pass from Mannion to Kevin Cummings, tying the score at 24.
WSU was trying to punt on its next possession when a bad snap gave the Beavers possession on the Cougars' 27. Brandin Cooks ran the ball in from 8 yards out to put Oregon State ahead 31-24 early in the fourth quarter.
Halliday was intercepted by Rashaad Reynolds on the first play of the ensuing series, giving the Beavers the ball in WSU territory. A 30-yard pass to Cooks gave the Beavers first down at the 1. Storm Woods ran the ball over for a 38-24 lead with 13:47 left in the game.
Washington State self-destructed in a slew of turnovers while Mannion connected on two touchdown passes to Cooks in the fourth.
The OSU-WSU rivalry is one of the longest in the Pac-12 at 98 games. Washington State leads the series 48-47-3.