Iannetta drove in Kole Calhoun with a two-out hit in the 11th inning off rookie Bobby LaFromboise, and the Angels rallied past the Mariners 3-2 Friday night for their eighth victory in 10 games.
Nick Franklin had three hits for the Mariners, who have lost 10 of 12 to fall 20 games below .500 for the first time this season.
Despite numerous opportunities to finish off the Angels with one big hit or even steady fielding, Seattle lost in walk-off fashion for the 13th time this season, tying the 2011 club record.
"We were one hit away quite a bit, and that's been an issue for us," Seattle manager Eric Wedge said. "You can look at Anaheim's veterans, but this is just where we're at in the process."
After Matt Shoemaker shut out the Mariners on two hits for five innings in his major league debut, Michael Saunders opened the scoring with a two-run single in the seventh for Seattle. Andrew Romine answered with a two-run single for Los Angeles later in the inning.
Erasmo Ramirez matched each of Shoemaker's zeros, twice stranding runners on third base and inducing two key double-play grounders while pitching six-hit ball into the seventh inning.
He only got into trouble after Kyle Seager's throwing error started Los Angeles' tying rally in the seventh. Shortly after Ramirez left with tightness in his groin, Romine delivered a solid two-out single off Chance Ruffin to tie it.
"I threw it away," Seager said. "That's pretty much the extent of it. I fielded it cleanly, gripped the ball and did the normal footwork, but it just took off on me. If the play gets made there, they don't score those two runs, and we'd be done a long time ago."
The Angels came back from a late two-run deficit and several missed opportunities to win the opener of their final homestand. Los Angeles has won 20 of 27 to move within three games of .500, even avoiding mathematical elimination from the playoff race for one more day.
"We're still working hard and trying to win some games at the end of the season," Iannetta said.
After Calhoun's one-out hit off LaFromboise (0-1), Seattle's sixth pitcher, Iannetta put a long single off the wall in deepest left-center. Calhoun slid home to give Iannetta his fifth career game-ending hit.
"He put a slider right over the plate, and I got a fortunate bounce (off the wall) to keep it in the yard," Iannetta said.
Cory Rasmus (1-1) pitched the 11th to earn his first major league victory.
Shoemaker, who turns 27 next week, made an impressive debut at Angel Stadium after a six-year minor league career.
The right-hander, who went 11-13 for Triple-A Salt Lake this season, got his big-league break on Thursday when Jered Weaver was scratched from his scheduled start with tightness in his right forearm. A few quick phone calls got his parents and wife into town in time for his debut, and he didn't disappoint.
"It was surreal, to say the least," Shoemaker said. "It's something you dream about your whole life, and then you finally have it. It was more fun than anything. If I wasn't nervous, I think there would be something wrong with me."
Seattle rallied in the seventh against Angels reliever Michael Kohn, whose step-slow coverage of first base on a two-out grounder allowed Dustin Ackley to beat it out. Saunders then delivered a single to center with the bases loaded.
The Angels stranded two runners in the eighth and again in the 10th. The Mariners intentionally walked Mike Trout in both innings to pitch to Josh Hamilton, who couldn't connect in either opportunity.
NOTES: Ramirez will be re-evaluated Saturday. ... Hamilton homered off Ramirez in the pitcher's major league debut early last season. ... Seager's Mariners-record streak of 106 consecutive starts at third base ended with the veteran sitting in favor of youngster Carlos Triunfel. Seager struck out as a pinch-hitter with two runners on in the seventh, and made a bad throw on Trumbo's grounder in the bottom half of the inning.