Larry Sanders scored 16 for the Rams (7-4), who lost for the first time in their last five games.
VCU was stubborn, trailing by just 32-31 late in the first half, but the Sooners went on an 11-0 run to take a 42-33 lead at the break.
The Rams ran off eight straight points to cut the deficit to four but Oklahoma went on an 18-5 run to go out in front to stay.
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