Kaleena Mosqueda-Lewis poured in a game-high 21 points as No. 3 Connecticut used a dominant second half to down fourth-ranked Duke, 79-49, at Gampel Pavilion.
Kelly Faris added a double-double with 18 points and 12 rebounds, while Breanna Stewart posted 13 points and five boards for the Huskies (17-1), who have won five straight since their lone loss of the season.
Alexis Jones paced Duke (16-1) with 14 points to go along with five rebounds and four assists.
Elizabeth Williams and Haley Peters followed with 11 points apiece as the Blue Devils dropped their sixth straight game against UConn to suffer their first defeat of the season.
Connecticut took a 32-30 edge into the break after a back-and-forth first half that saw seven lead changes and three ties, and then opened the second half with a 9-2 push to jump ahead, 41-32.
Chloe Wells halted the run with a shot from beyond the arc and Williams followed with a layup after a Stefanie Dolson jumper to bring the Blue Devils back within 43-37, but consecutive baskets by Mosqueda-Lewis sparked a lengthy 26-5 run by the Huskies to open up a 69-42 advantage with 6 1/2 minutes to play.
Connecticut's lead stretched as high as 31 from there as the Huskies cruised to the win, outscoring Duke by a 47-19 margin over the final 20 minutes.