Enhancing his MVP candidacy, Guerrero had four hits and figured prominently in three rallies, in the fifth, seventh and eighth innings.
Guerrero's double led to Garret Anderson's game-tying sacrifice fly in the fifth. His RBI double gave the Angels a 6-5 lead in the seventh, and his two-run single in the eighth followed Kendry Morales' go-ahead double to the opposite field against losing pitcher Brandon Morrow (3-3).
"In any situation, I don't change," Guerrero said, having driven his RBI count to 107 and his average to .326. "I know if I don't get it done, Garret Anderson is doing a good job, Gary Matthews ... we have other guys who can do it."
Stepping up on Tuesday night was native Cuban Morales, who is batting .450 in a five-game hitting streak since being summoned from Triple-A Salt Lake.
Morales' homer in the fourth, his third, came right behind a shot by Matthews (No. 17). These blasts jolted the Angels off the deck in the wake of Ervin Santana's dismal outing -- one out, five earned runs on four hits and two walks.
The comeback climaxed in the eighth when Matthews walked, stole second and scored on Morales' drive to left. Reggie Willits walked with two outs, and Cabrera singled. That brought Rick White in to face Guerrero, and Guerrero slammed his two-run single to left.
After an intentional walk to Anderson, Maicer Izturis extended his hitting streak to a season-high eight games with an RBI single, the inning ending with Guerrero thrown out at the plate.
"It seems we're starting to show some resilience," Matthews said. "We've had some come-from-behind wins, but to get that win, being down five, is tremendous for us. Huge game."
The Angels' comeback started with an unearned run in the third forced by Howie Kendrick's aggressive baserunning. Stopping the Mariners in their tracks was Moseley, with 5 1/3 innings of scoreless, two-hit relief.
"I'd put this right at the top," Moseley said. "This was a whole team effort all the way through. For all of us, this was a great situation to come out. We were looking to get two [wins], and we got there."
The Angels will go for a sweep on Wednesday against Mariners ace Felix Hernandez, with Jered Weaver getting the call.
The turnaround is swift, but the Angels figure to be riding a natural high after this dramatic comeback, matching their biggest rally of the season from a five-run deficit against Houston.
"I thought the biggest story was Moseley coming in and picking it up," Matthews said. "It's not easy to have to step in there spotting them a five-run deficit, but he did a great job for us."
Invaluable as a spot starter and in various relief roles as a rookie, Moseley showed his composure in his biggest test yet, stifling a lineup that had jumped all over Santana.
Ichiro Suzuki's leadoff triple started a five-run uprising that included Jose Guillen's two-run double, Adrian Beltre's two-run triple and Kenji Johjima's RBI single.
Throwing in the mid-90s but constantly behind in the count, Santana walked two hitters, and then he took a slow walk to the dugout.
Angels manager Mike Scioscia said he's unsure if Santana will get the call when his turn comes up next in the rotation and said that other options will be considered.
"We needed zeros to get back in the game," Scioscia said, "and Dustin did it. The middle innings were important, especially with the way they can shorten a game with their bullpen."
The Mariners never got to All-Star closer J.J. Putz, thanks to an uprising from the Guerrero-fueled attack, with Morales and Orlando Cabrera also major contributors with three hits apiece and Jeff Mathis (two hits, a walk) making his presence felt.
The Angels began their comeback with an unearned run in the third, courtesy of a throwing error by right fielder Jose Guillen on a single by Mathis. Kendrick, who'd walked, raced to third and came around to score as Guillen's throw bounded away from Beltre.
After Matthews and Morales delivered in the fourth, the Angels tied it at 5 in the fifth. Mathis doubled and scored on Cabrera's single. Anderson's sacrifice fly against southpaw Eric O'Flaherty scored Cabrera after Guerrero's double chased Weaver.
"I'm happy we picked up Ervin after what happened to him in the first inning," Guerrero said. "I looked around the dugout, and everyone was pumped up even though we were down [five runs]."
The Halos seized the lead in the seventh against reliever Sean Green when Guerrero crushed a two-out double to score Mathis, who'd walked. But the Mariners came back to tie it against Justin Speier when Yuniesky Betancourt doubled and scored on Ichiro's single.
"I was surprised they did that," Guerrero said, Mariners manager John McLaren having chosen to pitch to him with first base open and two outs. "I got something I could handle and ended up driving in a big run for us."
It was a show of respect to Anderson, who, since the All-Star break, has been among the most productive hitters in the game with 40 RBIs.
The win went to Speier (2-3), with Scot Shields delivering two innings of scoreless relief. Shields' return to form provided yet another brand of relief to Scioscia and Co. on a memorable night at Safeco Field.