Ashton Pankey finished with 18 points, nine rebounds and three blocked shots for Manhattan (12-10, 9-4 Metro Atlantic). Shane Richards scored 16 and grabbed seven rebounds and Rich Williams hit four 3-pointers and added 16 points, both career-highs.
Manhattan led 30-28 at halftime but opened the second with a 21-3 run to blow it open.
Canisius, which made just 19 of 61 (31 percent) field goals, including 5 of 18 (28 percent) from 3-point range, missed its first nine second-half field goal attempts and committed seven turnovers during Manhattan's decisive stretch.
A layup by Lewis capped an 11-2 run and pulled the Griffins within 67-62 with 2:32 left, but Manhattan made 11 of 12 free throws down the stretch to hold on.