Duke dominated California 45-21 in Week 6, with the Blue Devils controlling the game through a dominant second quarter and strong fourth-quarter finish. Duke quarterback Darian Mensah led the offense with 265 passing yards, connecting with receiver Cooper Barkate for 66 yards. Running back Nate Sheppard rushed for 91 yards and capped the victory with a 46-yard touchdown run in the fourth quarter.

California struck first with 14 points in the opening quarter, but Duke answered with 24 second-quarter points to seize control. The Golden Bears managed just seven more points in the second quarter before being completely shut out in the third and fourth quarters combined. Duke's defense recorded multiple crucial turnovers, including two interceptions of California quarterback Jaron-Keawe Sagapolutele in the second and fourth quarters. The game featured six lead changes and remained competitive early before Duke's offensive surge put the contest out of reach. Duke covered the 3.5-point spread while the game went over the 54.5-point total.