After a big win at Texas last week, Oklahoma (11-4, 2-1 in the Big 12) lost at Iowa State, 68-81, Saturday.
The last time that OU won in Hilton Coliseum was in 2011.
Brady Manek led OU with 17 points while Austi Reaves had 12 points and five rebounds.
Iowa State (8-7, 1-2) ended a three-game losing streak. OU played Kansas (12-3, 2-1) at home on January 15. In the past two years, KU has won at least one game in every Big 12 arena except for Lloyd Noble Center.