Griffin (6-6) yielded just a fifth-inning single to Devin Mesoraco and a Xavier Paul double in the seventh in dominating the Reds.
The right-hander posted his first victory since May 25, a span of five starts, allowing a pair of walks and striking out seven in the 108-pitch gem.
Donaldson, who belted a two-run homer in Tuesday's 7-3 Oakland win in the first game of the interleague set, delivered a three-run blast Wednesday, highlighting a four-run outburst in the fourth inning.
Reds starter Homer Bailey (4-6) was reached for four runs on six hits over six full frames.
Cincinnati fell for the fifth time in six games.