Quarterback Steve Slayden threw two touchdown passes and reserve tailback Stanley Monk rushed for two scores as the Blue Devils won at home.
Northwestern cut Duke's lead to 24-17 on John Duvic's 36-yard field goal with 8:43 left in the third quarter, but Duke came back with two touchdowns in a six-minute span to win the first game between the teams.
Slayden, who completed 21 of 28 passes for 229 yards without an interception, found tight end Jason Cooper for a two-yard touchdown pass with 2:16 left in the third quarter to make the score 31-17.
After a 15-yard penalty for pass interference on the touchdown, Duke kicker Ken Harper recovered his onside kick at the Northwestern 33. Reserve fullback Eric Sanders scored on a four-yard run seven plays later to make it 37-17. Harper missed the extra point, ending his streak of 35 straight conversions.
Harper made a 27-yard field goal with 7:25 left for the final score.
Monk, who led the Blue Devils with 86 yards rushing, scored on runs of 16 and three yards in the second quarter as Duke built a 24-14 halftime lead.
John El-Masry, a starting defensive end for Duke, has been suspended from the team for his involvement in an assault on another Duke student, according to university officials.
El-Masry appealed his suspension Thursday night to the university president, who failed to overrule a university board that had earlier recommended he be suspended from the team for his role in the assault last February on Alexander Van Dyne.