The Panthers had taken a 56-55 lead on two free throws by Talib Zanna with 4.4 seconds left, but Ennis answered with a 35-foot heave that swished through just before time expired, allowing the Orange (24-0, 11-0 ACC) to extend the best start in school history.
Ennis netted 10 of his 13 points in the second half.
C.J. Fair also came big down the stretch, collecting 10 of his 14 points after the break.
Zanna provided 16 points and 14 rebounds for Pittsburgh (20-5, 8-4).