In midst of that final 20 minutes, OU shot only 29.6 percent, but it was point guard Danielle Robinson that sealed it up down the stretch by avenging a miss on a crucial one-and-one opportunity earlier in the season by hitting four key free throws along with a pair from center Joanna McFarland.
That helped to push OU over the top after trailing 62-59 in the final minute.
The Sooners took control in the first half and snuck out to a 14-point intermission advantage at 38-24.
They did that behind 50 percent shooting from the field, but that plummeted in the second frame, as OU finished just 40.4 percent for the game.
ISU actually outshot OU, converting 49 percent of their shots, but it was turnovers and free throws that key this one.
The Sooners turned it over just 10 times to 24 for the Cyclones, while they were 87.5 percent (14-of-16) from the line, while the visitors were 70 percent (7-of-10) there.
Guard Kelsey Bolte led all scorers with 23, and guard Hannah Christopherson added 14.