Acquired a day earlier in a trade with the Chicago White Sox, Dunn became the 12th player in Oakland history to homer in his first at-bat with the team.
Dunn homered during a five-run first inning. His drive was a welcome sight for a team that just got swept in a four-game series by the AL West-leading Los Angeles Angels and was shut out for 29 straight innings.
The A's broke loose a day after manager Bob Melvin let them have it in a closed-door team meeting. He called his team's play "embarrassing and "pathetic" after the A's totaled just four runs in the sweep at Anaheim.
Dunn went 2 for 3 batting cleanup as the designated hitter. He provided a nice lift for an Oakland offense that has struggled since dealing Yoenis Cespedes to Boston for Jon Lester on July 31.
With 461 career home runs, Dunn tied Red Sox star David Ortiz for 35th place on the all-time list.
Dunn quickly staked Jason Hammel (2-5) to a lead. Hammel also started the season in Chicago, and was traded by the Cubs in July.
Hammel allowed three hits and struck out five in eight innings to end a three-start winless stretch. It was just his second win since joining the A's from the Cubs on July 4.
Josh Willingham was the last A's to homer in his first at-at-bat on April 1, 2011.
Another recent acquisition, Geovany Soto, added a two-run single with two outs in the first that chased Chris Young (12-7) for the shortest start of his career.
A sellout crowd of 36,067 saw the A's win after a stretch in which they lost five of six.
Brad Miller homered leading off the sixth for Seattle, which came into the series opener as the American League's top road team.
Robinson Cano's 21-game hitting streak against the A's ended. It dated to Sept. 22, 2012.
Mariners: OF Michael Saunders, on the disabled list since July 11 with a strained left oblique, reported to Arizona to work on strengthening and get some at-bats in simulated games before the club determines the next step in his rehab.
Athletics: CF Coco Crisp will have more trigger-point injections for neck stiffness after colliding with the outfield wall Friday.
Mariners: LHP James Paxton (4-1, 1.83) makes his first career appearance against the A's as he looks to win his second straight start. Paxton is 7-1 with a 1.71 ERA in 11 career starts.
Athletics: RHP Sonny Gray (13-7, 3.03) is 4-0 with a 1.10 ERA in his first five starts against Seattle, his most victories against any team.