The Buffs went for the first on fourth-and-10 from the Washington State 28-yard line, and under heavy pressure, quarterback Steven Montez scrambled to find an open receiver, but threw an incomplete pass. During the play, Irwin blindsided Cougars defensive tackle Derek Moore to draw the flag.
"That was a stupid play by him," head coach Mike MacIntyre said.
Because the penalty occurred in the first half, Irwin will not have to sit out any of the next game.
This is the third targeting penalty against the Buffs this season. Safety Afolabi Laguda and defensive tackle Chris Mulumba were both ejected from the Sept. 16 game against Northern Colorado for targeting.
In addition to losing Irwin in the first half, the Buffs lost center Jonathan Huckins and cornerback Isaiah Oliver to injuries in the game.
Oliver appeared to suffer a leg injury on Washington State's first touchdown, early in the second quarter and never returned. After the game, CU said Oliver would be evaluated on Sunday in Boulder.
Huckins suffered a concussion. Combined with Irwin's ejection, that forced the Buffs to shuffle their line.
Josh Kaiser and Isaac Miller both played at left tackle, and Miller and Aaron Haigler both played at right tackle. After Huckins went down, Tim Lynott Jr. moved from right guard to center, and Brett Tonz played at right guard.
Outside linebacker Derek McCartney was shaken up after a play midway through the first quarter, but he returned in the second half. Reserve defensive lineman Timothy Coleman Jr. was also being treated by trainers in the first half, with an apparent foot injury.
Nose tackle Javier Edwards returned Saturday after missing last week's game at Oregon State with an ankle injury. On his first play of the night, he forced a fumble that CU's Evan Worthington recovered.
"Definitely, it always feels good to be back," Edwards said. "I felt great."
CU has lost 28 consecutive road games against ranked teams, with the last victory coming on Sept. 21, 2002, at UCLA. ... Despite a bad night, Montez has thrown 108 consecutive passes without an interception - the sixth-longest streak in CU history. ... CU nearly went the whole game without a turnover, until Juwann Winfree had a fumble with 3:11 to play in the fourth quarter. The Buffs came in with a school-record three consecutive turnover-free games. The Winfree fumble snapped a streak of 16 consecutive quarters without a turnover for CU. ... After recording one sack in the first four Pac-12 games, the Buffs had two on Saturday, one by McCartney and another shared by Leo Jackson III and Chris Mulumba. Devin Ross, who had no catches in the previous two games, led CU with four catches for 27 yards. ... The Buffs went 1-for-17 on third down conversions. The only conversion came on the meaningless final play of the first half.
Contact staff writer Brian Howell at email@example.com or twitter.com/BrianHowell33.