Halliday, a senior, completed 41 of 62 passes and was intercepted twice. Washington State piled up 706 yards of offense while holding Portland State to 362 yards.
Dom Williams caught four passes for 112 yards and two touchdowns for the Cougars.
Halliday came into the game leading the nation with 921 passing yards.
Washington State has never lost to an FCS opponent and the Cougars scored on three straight possessions, starting late in the first quarter, to take control.
Washington State's Gerard Wicks powered over from the 1-yard line, completing an 80-yard drive in 14 plays. The drive featured nine catches or rushes by the WSU running backs, which coach Mike Leach said this week was essential for his Air Raid offense to have success.
Portland State drove down to the WSU 10 on its next possession. But running back Shaq Richard fumbled and Washington State's Destiny Vaeao recovered on the 7 to kill the drive.
Halliday connected with Myers on a 67-yard pass play. Five plays later Halliday fired a 15-yard touchdown pass to River Cracraft in the end zone and Washington State led 14-0 early in the second quarter.
Portland State was forced to punt on its next possession, and Rickey Galvin returned the ball 44 yards to the PSU 17. Halliday on the first play connected with Dom Williams, who ran into the end zone for a 21-0 WSU lead.
Portland State got the ball on downs at Washington State's 44, but McDonagh was intercepted in the end zone by Charleston White to end the threat. Washington State marched 80 yards in six plays, with Halliday hitting Vince Mayle in the end zone for a 28-0 lead that stood at halftime.
Halliday had 321 passing yards and three touchdowns in the first half, while Myers caught seven passes for 150 yards in the first. Portland State was held to 119 total yards in the first half.
Portland State finally got on the scoreboard on the first series of the second half. Richard scored on a 7-yard run, capping an 11-play, 85-yard drive, to cut WSU's lead to 28-7.
After a Washington State punt, the Vikings marched 71 yards in six plays. McDonagh completed the drive with a 24-yard touchdown pass to Kasey Closs in the end zone as Portland State cut WSU's lead to 28-14.
Washington State replied with a 75-yard drive that ended with Halliday's 8-yard touchdown pass to Myers, for a 35-14 lead late in the third. Myers caught a 4-yard touchdown pass from Halliday on WSU's next possession for a 42-14 lead.
Halliday was intercepted by Patrick Onwuasor, who returned the ball 42 yards for a touchdown, but Portland State still trailed 42-21 with 13:19 left in the game.
Halliday and Myers connected on a 55-yard touchdown pass midway through the fourth.
This is Portland State's second game against a Pac-12 team this season. It lost 29-14 at Oregon State on Aug. 30, after leading at halftime. The Vikings dropped to 2-32 all-time against FBS schools, including 0-14 against Pac-12 schools.
Portland State piled up 507 yards of offense in edging lower-division Western Oregon 45-38 last week, but couldn't get untracked against the Cougars.