Seager homered for his second straight at-bat after being mired in a slump for most of the season. Seager hit a two-run homer in the seventh off Houston starter Jarred Cosart, then added the winning shot on the first pitch from Josh Fields (0-1) in the ninth. The five RBIs were a career high for Seager.
Seattle opened the ninth with a single from Robinson Cano that fell in front of Houston's outfield that was playing deep and a sharp single by Corey Hart.
Fernando Rodney (1-1) got the victory, pitching the top of the ninth in relief.
Seattle's late rally spoiled what was looking to be a sweep for the Astros.
Cosart took a shutout into the seventh after failing to make it out of the first inning in his previous start. The Astros got a two-run double from Jason Castro in the third inning and Chris Carter's second homer of the series in the seventh to take a 3-0 lead.
But that was all erased by Seager, who entered the day hitting .156 with just two RBIs on the season.
Seattle cut the lead to 3-2 in the bottom of the seventh when Justin Smoak singled to left against the shift and Seager followed with his first homer of the season. Cosart was replaced and Houston's relievers got to the ninth without issue and Fields taking over.
Fields had earned saves in the first two games of the series, but was battered by Seattle this time. Cano opening the ninth inning with his single, followed by a line drive to left from Hart. Fields rallied to strike out Smoak, but Seager jumped on the first pitch and hit it out deep to right field.
It was the third multi-homer game of Seager's career.
Houston got its first two runs because of Seattle starter Chris Young's struggle with control. Young finished with five walks, including a trio in the third inning. Young walked Matt Dominguez on a 3-2 pitch to start the inning, then did the same to Dexter Fowler with two outs. Castro followed with a line drive just fair down the right-field line that allowed both runners to score.
Houston added another in the seventh when Carter hit his second homer of the series, a solo shot that just cleared the wall in left field. The homer came on a 3-2 pitch moments after Seattle manager Lloyd McClendon and a trainer had come to the mound to check on a possible injury. Young had retired 11 of 12 batters prior to the Carter homer.
Despite getting a no-decision, Young provided a break for Seattle's taxed bullpen by making it through seven innings throwing 113 pitches. He struck out six and walked five.
NOTES: Seattle RHP Taijuan Walker (shoulder) and LHP James Paxton (back) will begin recovery throwing programs within the next week. McClendon said Paxton has been cleared to start throwing Friday and Walker next Monday.