David Stockton added 10 points, five assists and five rebounds while Przemek Karnowski had 10 points and six rebounds for the Bulldogs (25-6, 15-3 West Coast Conference). Coach Mark Few's team had previously clinched the regular season title and will head into the conference tournament as the top seed.
Dower, limited to six points because of foul trouble in Thursday's win over Pacific, went 7 of 11 from the floor and helped spark an early 21-3 run for Gonzaga.
The Zags led by as much as 34 and outscored the Gaels 42-14 in the paint.
Stephen Holt had 10 points, all on free throws, for St. Mary's (21-10, 11-7).
Dower, who has seven of his eight career double-doubles this season, was coming off a back injury and didn't score in seven minutes when the two teams played on Jan. 2. He had no health issues this time, scoring on a series of mid-range jumpers in the first half, then powering in for a thunderous dunk early in the second half.
The game drew a standing-room-only crowd to McKee Pavilion for Senior Night and was televised nationally, reminiscent of previous clashes between these two longtime rivals.
It wound up a lopsided blowout by the Bulldogs, who built a 20-point halftime lead then cruised to their sixth straight win over the Gaels.
Gonzaga will take a much-deserved break after playing its fourth game in 10 days. The Bulldogs open the WCC tournament against the winner of Thursday's game between Pacific and Santa Clara.
The Bulldogs will do so on the heels of a rare blowout in this series between the two conference giants.
St. Mary's, which plays Pepperdine on Saturday, led 3-0 on Beau Levesque's 3-pointer before Gonzaga went on a 21-3 run over the next eight minutes.
The Bulldogs led by double digits the rest of the way while helping Few earn his 399th career win.
Dower nearly had his double-double before the break. He had nine points and seven rebounds while scoring on a pair of mid-range jumpers, a layup and a put-back.
Gonzaga also got an early lift from its backcourt tandem of Kevin Pangos and David Stockton. The duo repeatedly gashed the Gaels with drives down the lane and helped the Bulldogs open a 15-point lead following their big run in the first half.
St. Mary's, which ended Gonzaga's stranglehold on the conference regular season championship with back-to-back titles in 2011 and '12, had no answer on either end. The Gaels shot just 19 percent before halftime and had scoreless stretches of 6:24 and 5:18.