Webb (3-3) gave up six hits, struck out four and walked a batter. The Reds left the bases loaded in the second inning, but Webb didn't allow a runner past second for the rest of his outing and induced a pair of double-play balls.
The Reds didn't help themselves defensively.
In the Giants fourth, shortstop Eugenio Suárez misplayed a grounder that allowed Brandon Crawford to reach. Flores followed with his third home run of the season, a shot into the first row of the right-field stands.
Yastrzemski hit a 430-foot homer to right-center field with two outs in the fifth, and Dubón pushed it to 5-0 with a two-out solo shot in the sixth.
Gray went five innings, allowing five hits and four earned runs with three strikeouts.
Reds 3B Mike Moustakas didn't start for the third straight game after suffering a heel contusion during the series in Colorado. He pinch-hit in the eighth inning, drawing a walk. Manager David Bell said he could return to the lineup as soon as Tuesday. Moustakas had been playing first base with Joey Votto sidelined by a fractured thumb.
Giants RHP Anthony DeSclafani makes his first appearance at Great American Ball Park on Tuesday since signing with San Francisco in the offseason. He spent five seasons with Cincinnati. The Reds will counter with right-hander Luis Castillo.
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