Tiffany Hayes poured in a game-high 23 points to ranked 55, on Monday.
Bria Hartley had 20 points and seven rebounds, while Stefanie Dolson and Kaleena Mosqueda-Lewis donated 10 points apiece for the Huskies (24-2), who have won 12 consecutive games.
Whitney Hand paced the Sooners (16-8) with 18 points and six rebounds and Sharane Campbell finished with 11 points and seven rebounds. Jelena Cerina contributed seven points and nine rebounds for the Sooners, who had won four of five coming in.
UConn got off to an incredibly hot start, jumping out to a 21-4 lead with under 12 minutes to go in the first half.
Oklahoma responded with an 11-0 run to get within 21-15, capped by four free throws by Campbell, but UConn kept the pressure up and took a 37-28 lead into the locker room at halftime.
The Huskies shot just 40 percent from the floor and were led by Hartley and Hayes with 12 points apiece. UConn was also stellar on the defensive end, holding the Sooners to just 30 percent from the floor.
The Sooners picked up the offense slightly in the second half, shooting 39 percent from the floor, but never got closer than seven.