Luke French (5-6) allowed eight hits and two runs over five-plus innings for the win.
James Shields (13-14) was charged in the loss for eight hits and five runs over six full frames.
The Mariners forged ahead for good in the sixth, when a Justin Smoak single and walk to Mangini preceded the tie-breaking three-run homer from Wilson.
Mangini’s seventh-inning RBI single boosted the Mariners to a 6-2 edge, then Jamey Wright spelled French with two scoreless innings of relief.
Seattle snapped a scoreless tie in the fifth, as a walk to Ichiro Suzuki and double by Chone Figgins preceded a two-run single from Lopez. Tampa Bay responded during its at-bat, tallying twice on an RBI triple from Jennings followed by a run-scoring hit from Upton.
When Shields gave up Wilson’s blast, it was the 34th homer he surrendered this season, breaking Tanyon Sturtze’s previous team record of 33 home runs set back in 2002…Despite the loss, Tampa Bay won the season series, 7-2, but lost both games at home.