Jack-of-all-trades Brandon Connette ran for one score and threw for another, and Ross Cockrell returned a blocked field goal 75 yards for the TD that capped the Blue Devils' most productive quarter since 1999.
Renfree was 21 of 30. Conner Vernon had 10 catches for 180 yards and a 28-yard TD, and set a school record with his 208th career reception.
Duke opened by beating a Football Bowl Subdivision team for the first time since 2002. The Blue Devils led 44-14, improved to 3-2 in openers under David Cutcliffe and snapped a seven-game losing streak that dated back to last year's victory over FIU.
Kedrick Rhodes rushed for 130 yards and had a 67-yard touchdown catch and a short, late scoring run.