Iwakuma (12-6) allowed three runs on seven hits over seven innings to notch a second straight win following a 3-1 victory over Texas last week. The right-hander walked two and struck out four.
Danny Farquhar struck out the side in the ninth for his ninth save as the Mariners took the rubber match of a three-game series.
The score was tied 2-2 with two out in the fifth when Miller pounded a 1-0 pitch from A.J. Griffin over the right-field fence for a solo shot, putting the Mariners ahead to stay.
Brendan Ryan went 2-for-4 with three RBI and Mark Morse added a bases-empty home run for Seattle.
Griffin (10-9) surrendered four runs on five hits over six innings for the A's, who came into the contest trailing American League West-leading Texas by 1 1/2 games.