Chicago, IL – Kaleena Mosqueda-Lewis scored 25 points and 44.
Tiffany Hayes netted 14 points with four assists while Stefanie Dolson and Bria Hartley added 10 points apiece for Connecticut (17-2, 6-1 Big East), which has won five straight games since falling to Notre Dame on January 7.
Brittany Hrynko led DePaul (15-5, 3-3) with 18 points.
UConn shot 53.3 percent and made 6-of-11 from beyond the arc in the opening half to take a commanding 53-23 advantage into the locker room.
UConn led by as many as 45 in the second half.