Leadoff hitter Dee Gordon went 3-for-4 with a double and scored twice for the Mariners, who took two of three games in the series.
Oakland ace Sean Manaea (4-3) had his worst start of the season.
Manaea, named the American League's Pitcher of the Month for April, allowed four runs on six hits in six innings, with five strikeouts.
In six previous starts, Manaea had allowed a total of five earned runs and no more than two in any game, going 4-1 in the first month and throwing a no-hitter against the Boston Red Sox.
The Mariners got to Manaea early thanks to Gordon, who is 16-for-23 (.696) over the past five games.
Gordon led off the bottom of the first with an infield hit off the glove of Oakland first baseman Matt Olson. Gordon stole second, advanced to third on a bunt by Jean Segura and scored on Robinson Cano's single to left field.
Gordon led off the third with a bloop double down the right-field line. He went to third on another bunt by Segura and scored when Cano lined a single to center field.
Cruz then hit a 1-0 pitch over the center-field fence, giving Seattle a 4-0 lead. It was Cruz's seventh home run of the season.
Seattle left-hander Wade LeBlanc, making his first start since late in the 2016 season, pitched four scoreless innings. LeBlanc allowed three hits, walked one and struck out three.
The Athletics scored their only run when Stephen Piscotty led off the fifth by launching a 443-foot homer to left-center field off reliever Chasen Bradford. It was Piscotty's second home run of the season.
Bradford (3-0) pitched 2 1/3 innings of one-hit relief for the victory. James Pazos recorded the final two outs in the seventh.
Juan Nicasio struck out the side in the eighth and Edwin Diaz pitched the ninth for his major league-leading 13th save.
--Field Level Media
Oakland | Seattle | |
Sean Manaea | Player | Wade LeBlanc |
Loss | W/L | No Decision |
6.0 | IP | 4.0 |
5 | Strikeouts | 3 |
6 | Hits | 3 |
6.00 | ERA | 0.00 |
Oakland | Seattle | |
Jed Lowrie | Player | Dee Gordon |
2 | Hits | 3 |
0 | RBI | 0 |
0 | HR | 0 |
2 | TB | 4 |
.500 | Avg | .750 |