Calhoun singled with one out in the 11th and was still on first after Seattle reliever Bobby LaFromboise got the second out. Iannetta worked the count to 2-2 before hitting a drive off the wall in left-center.
Calhoun, off with the hit, scored all the way from first to end the game.
LaFromboise (0-1) allowed just those two hits in 1 1/3 innings of relief but took the loss. It was his first major-league decision.
The Angels' Cory Rasmus (1-1) struck out the first two batters he faced and got the third on a grounder in the top of the 11th for his first major-league win.
The rest of the game's scoring came in the seventh inning. The Mariners broke the 0-0 tie with a two-run single by Michael Saunders only to have the Angels counter with a two-out base hit by Andrew Romine that drove in Mark Trumbo and Calhoun.