Devon Saddler scored 15 for Delaware (23-9), Kyle Anderson 12, and the Fightin' Blue Hens forced 15 turnovers.
Hofstra (10-23) dominated the boards, out-rebounding Delaware 39-28, including 17-8 offensive rebounds.
The Pride took an early lead but Delaware tied it at 32 when Saddler capped a 10-2 run with a pair of free throws. Hofstra surged ahead on back-to-back treys by Zeke Upshaw and led 40-37 at halftime.
Delaware opened the second half with a 13-2 run in which Usher sank two 3s, then led 79-67 after an 8-2 run capped by a Carl Baptiste dunk. Delaware hit seven free throws in the final minute to clinch the win.
Upshaw led Hofstra with 23, Dion Nesmith scored 16 and Stephen Nwaukoni 13. Jordan Allen grabbed 10 rebounds.
Delaware will play fifth-seeded Northeastern in the semifinals on Sunday.