The returning Heisman Trophy winner, who missed his team's first two games with a left knee injury, rushed for 151 yards on just nine carries.
Greg McElroy went 14-of-20 through the air for 258 yards, racking up three touchdowns and one interception for Alabama (3-0).
Julio Jones hauled down five passes for 106 yards with a touchdown and Trent Richardson chipped in 61 yards on the ground, including a 45-yard scoring run and a kickoff returned for a touchdown.
Duke (1-2) was led by Sean Renfree, who tossed for 144 yards with a touchdown. The Blue Devils fell to 0-11 all-time against No. 1 teams with the setback.