Josh Perkins added 13 points, six rebounds and five assists for the Bulldogs (17-5, 9-2 West Coast Conference), who stretched a 17-point halftime advantage to their largest lead at 84-43. Bryan Alberts scored 10 points and Kyle Dranginis grabbed 10 rebounds.
Gonzaga shot 15 of 37 from 3-point range with Melson sinking five and Wiltjer and Perkins adding three each.
Uche Ofoegbu led the Dons (11-10, 5-6) with 16 points and Devin Watson scored 11.
The Bulldogs opened with an 8-0 run and had a 14-point lead before the midpoint of the first half. San Francisco cut it down to six before Gonzaga closed the first half with an 11-0 run to lead 39-22.
When Gonzaga beat the Dons 102-94 in overtime on Jan. 3 in San Francisco, it needed a late rally to overcome a 16-point, second-half deficit.