After trailing at halftime, Taylor Robertson scored 19 of her 22 points and Madi Williams scored 12 of her 19 points in the second half to secure the Sooners victory.
“We beat a really good team today,” said Oklahoma head coach Sherri Coale. "Iowa State is very volatile offensively … I thought our attention to defending all of their stuff was really good."
Robertson's performance marks her seventh straight game with scoring 20 points or more.
Gabby Gregory added 16 points for the Sooners. Mandy Simpson had 12 points, eight rebounds and four assists.
Oklahoma moves to 9-6 overall and 2-1 in conference play.