Colt Hynes came in to pitch, but Davis greeted him by golfing a 2-0 pitch deep into the right field seats for a mammoth three-run shot, his major league-leading 41st of the season.
The Orioles ended up scoring four runs in the eighth, completing a two-game interleague series sweep.
J.J. Hardy smacked a solo homer and drove in three runs while Adam Jones went 3-for-5 with two runs scored as Baltimore improved to 4-2 in August.
Francisco Rodriguez (1-0) earned the decision in relief of starter Miguel Gonzalez, who surrendered three runs on six hits over six innings.
Jedd Gyorko cracked a three-run homer for the Padres.
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