In the first game between the two schools, the Mountaineers (6-5, 3-5 Big 12) trailed 24-23 when they took over on their own 25 after Iowa State's Edwin Arceo kicked a 49-yard field goal.
Smith took the snap in shotgun formation and immediately flicked the ball to Austin cutting in front of him. Austin, who had been held in check until then, turned the corner and easily outran the pursuit down the left sideline.
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Iowa State (6-6, 4-5) then drove to the West Virginia 7, but Jeff Woody fumbled into the end zone and Karl Joseph recovered for the Mountaineers, which ran out the clock.
West Virginia became bowl eligible for the 11th straight season with the victory and could enhance its postseason position with a victory over Kansas at home in its regular-season finale next Saturday. The Mountaineers' losing streak had been their longest since dropping six in a row in 1986.
Iowa State played its regular-season finale and will await its third bowl bid in coach Paul Rhoads' four seasons.
Both teams put up decent numbers despite raw, blustery conditions. The wind blew at a steady 15 mph out of the northwest and the wind chill was 21 degrees at kickoff.
Smith fell well short of his 336-yard passing average, but still completed 22 of 31 for 236 yards and two touchdowns. He worked against an Iowa State secondary missing injured starters Jansen Watson and Durrell Givens, the national leader in takeaways.
Austin was held to 74 yards rushing in 14 carries after gashing Texas for a school record 344 yards last week. But the power running of 5-foot-11, 235-pound Shawne Alston helped keep the Mountaineers moving.
Alston carried 19 times for a career-best 130 yards and a touchdown and helped his team play keep-away at the end.
Iowa State freshman Sam Richardson, making his first start after throwing four touchdown passes in a relief role at Kansas last week, completed 13 of 31 passes for 162 yards and three touchdowns. Often forced out of the pocket, he showed some nimble feet in scrambling for 119 yards in 18 carries.
Neither quarterback was intercepted and despite the frigid conditions, there were no fumbles until Woody's near the end.
With Iowa State leading 21-20, a holding penalty negated Austin's 68-yard touchdown on a punt return. The Mountaineers ending up settling for a field goal, Tyler Bitancurt coaxing through a 35-yarder that nicked the left upright for a 23-21 lead with 9:35 left. Bitancurt had missed a 46-yard attempt in the first quarter when the ball hit the left upright and bounced back onto the field.
Iowa State had taken its first lead of the game at 21-20 when Richardson hit Quenton Brundage in stride for a 35-yard touchdown with 4:56 left in the third quarter. They hooked up six plays after the Mountaineers went up 20-14 on Bitancurt's second field goal of the game, a 44-yarder.
West Virginia chipped away at the Iowa State defense on a time-consuming drive that stalled after a holding penalty at the Cyclones' 33. Cleyon Laing's sack of Smith on third down forced the field goal.
After West Virginia managed only a 3-0 lead with the wind at its back in the first quarter, Smith took the Mountaineers on two snappy touchdown drives against the wind in the second period.
He completed passes of 27 and 23 yards to Steadman Bailey before Alston wedged into the end zone from a yard out to make it 10-0. The next time Smith and his teammates got the ball, he finished a 70-yard, eight-play drive with a 6-yard touchdown pass to Bailey, who beat Givens' replacement, Gage Shaeffer, on a square out.
But Iowa State and Richardson answered both scores.
Richardson found Jerome Tiller in the back left corner of the end zone for an 8-yard touchdown to cut the lead 10-7.
Then, taking over at the Iowa State 29 with just 1:32 left in the half, Richardson executed the 2-minute offense to perfection. He converted a third-and-10 with an 18-yard pass to Jarvis West and scrambled for 21 yards on fourth-and-6 from the West Virginia 39.
On the next play, Richardson hit Josh Lenz, who made a shoe-top catch for an 18-yard touchdown with 18 seconds left in the half, drawing the Cyclones to 17-14.