The Mariners, who entered the day tied with Kansas City and Tampa Bay for the second AL wild card, finished 6-3 on their road trip.
Cruz hit a two-run homer in the third, his 25th, then added his 26th in the fifth. It's the second multi-homer game in four days for the Mariners slugger, who has 22 RBIs in 13 games against the A's this season.
Seager homered in the first inning after Jean Segura and Cano singled.
All three home runs came off Oakland starter Jharel Cotton (5-9).