Jaxon Shipley caught eight passes for 137 yards and Mike Davis had 113 receiving yards and a touchdown for the Longhorns (8-2, 5-2 Big 12), who won their fourth straight game.
Jonathan Gray scored twice on 14 carries and Joe Bergeron led Texas in rushing with 86 yards on 12 carries.
Texas rolled up 609 yards of total offense and held Iowa State (5-5, 2-5) to 277 yards.
The Cyclones were 3-for-12 on third down conversions in losing their second consecutive game.
Steele Jantz completed 15-of-29 passes for 133 yards and a touchdown, but was picked off twice. He connected with Quenton Bundrage on 14-yard TD pass with 41 seconds to play in the first half for Iowa State's only points.