The home runs erased a stellar start by Jon Lester (13-10) and helped Mariners ace Felix Hernandez (14-5) win for the first time in four outings.
Adam Dunn homered in the fourth for the only run Hernandez allowed in eight innings. Hernandez gave up three hits, struck out four and walked two to outduel Lester in a matchup of two of the AL's best pitchers. The Mariners tagged Lester for seven hits in eight innings.
Fernando Rodney pitched a perfect ninth for his 41st save in 44 chances.
The A's have lost seven of nine, including a four-game series at the AL West-leading Los Angeles Angels before dropping two of three to Seattle at the Coliseum. The Mariners remain right behind Detroit and Oakland in the chase for the AL's two wild cards.
The series finale served as a possible preview for that wild-card matchup — including the starting pitchers and the ballpark that could host the game.
And for most of the sun-touched afternoon, the starters lived up to the hype.
Hernandez, who allowed a career-high four home runs in his last start against the Washington Nationals, returned to his dominant ways for all but one pitch. Dunn hit his second homer in three days since being traded from the Chicago White Sox, keeping a fastball inside the right-field foul pole to put Oakland ahead in the fourth.
Dunn's drive was his 22nd homer this season and 462nd of his career, tying him with former A's slugger Jose Canseco for 34th in major league history.
Lester looked to be in his All-Star form, scattering hits and keeping batters off balance, but Seattle changed that on the left-handers first three pitches of the seventh.
Seager and Hart hit back-to-back homers to give the Mariners the lead. It was Seager's 22nd home run this season, tying a career high, and Hart's fifth.
The A's never got anything going late. The Mariners retired the final 11 Oakland hitters, and A's first baseman Stephen Vogt was replaced in the seventh after spraining his left ankle.
Mariners: Chris Young, chased Monday after getting just two outs in the shortest outing of his career, threw a bullpen session and felt fine. Manager Lloyd McClendon will decide Thursday whether the 35-year-old right-hander will make his next start Saturday.
Athletics: CF Coco Crisp felt better after receiving trigger-point injections Wednesday to help relieve tightness and pain in his neck. He could return to the lineup Friday. ... Reliever Sean Doolittle (strained right intercostal) played long toss. He will take Thursday off and resume his rehab Friday. ... INF Nick Punto (hamstring) got a cortisone shot earlier in the week and will try running sprints Friday.
Mariners: LHP Roenis Elias (9-12, 3.97 ERA) starts the opener of a four-game series at Texas on Thursday. He's 1-1 with a 2.60 ERA in three starts against the Rangers.
Athletics: After an off day Thursday, RHP Jeff Samardzija (4-4, 3.57 ERA) starts the opener of a three-game series against Houston. He has gone eight innings in his last two starts.