It was the first-ever matchup between the two schools, which are located a couple of miles from each other.
Lewis finished with 189 yards passing for the Blue Devils (2-2), who totaled 486 yards on offense. Freshman Desmond Scott led Duke with 100 yards rushing and a touchdown on 16 carries, while Patrick Kurunwune added 93 yards on the ground and a score on 14 attempts.
The Blue Devils scored on their first three possessions to claim a 21-0 lead. North Carolina Central (0-4) scored two touchdowns - Tim Shankle's 1-yard run and Jeffery Henderson's 83-yard interception return, cutting the margin to seven.
But Duke responded with 28 unanswered points to pull away from the Eagles.