Trout’s three-run homer in the third inning off Mike Montgomery (4-3) erased a 1-0 deficit. He opened the seventh with a solo shot, tying him for the league lead at 26 with teammate Albert Pujols.
Cron opened the fourth with his fourth home run and then hit the first pitch from reliever Danny Farquhar for a two-run shot in the sixth to make it 6-1.
Mark Trumbo hit a two-run homer for Seattle in the ninth off Vinnie Pestano, called up from Triple-A Salt Lake earlier in the day.
The Angels won for the sixth time in seven games to pull within a half-game of first-place Houston in the AL West. The Astros lost to Tampa Bay 3-1, their fourth straight defeat.
Santiago (6-4), who escaped the first inning allowing one run despite three hits, struck out seven and walked none.
Montgomery, who had allowed just one run in 23 2-3 innings in his last three starts, was tagged for five runs and eight hits in five innings.
Trout put the Angels up 3-1 in the third with his 25th homer. Johnny Giavotella doubled with one out and Kole Calhoun was hit by a pitch. Trout then lined a 1-0 pitch deep over the wall in center field.
The Mariners took a 1-0 lead in the first when Franklin Gutierrez singled with one out and then hustled to second on Robinson Cano’s fly out to deep center. Nelson Cruz then punched an RBI single just beyond the reach of shortstop Erick Aybar.
Kyle Seager doubled and Cruz went to third, but Santiago retired Trumbo on a pop out to first.
Angels: LHP C.J. Wilson (7-6, 3.82 ERA) is 4-1 in his last five starts. In two starts against the Mariners this season, he has allowed two earned runs in 15 innings. Wilson has pitched at least six innings in eight of his last nine starts.
Mariners: RHP Hisashi Iwakuma (0-1, 7.17) will be making his second start since coming off the DL. Iwakuma, who had been on the DL since April 24 with a strained lat muscle, allowed five runs and eight hits —including four home runs — in five innings in his first start back on Monday, a 12-5 loss to Detroit.
Angels: Closer Huston Street, who injured his right groin on Wednesday, will not pitch again before the All-Star break, but will not be placed on the DL. “He feels even better today than he did yesterday,” manager Mike Scioscia said before Friday’s game. “We’re going to let this thing play out through the All-Star (break) and then we’ll have a decision. But right now, I think we want to keep in play the option that he’s not sitting on the DL for a week when he’s ready to go.”
Mariners: CF Austin Jackson, who left Wednesday’s game against Detroit with back spasms, said he’s improving, but was waiting to see how he felt after swinging a bat before Friday night’s game. “If it feels good in the cage, probably go out and try to take a round or two of BP,” Jackson said. With the additional time off with the pending All-Star break, manager Lloyd McClendon said there was no need to rush Jackson back. “I won’t unless he tells me tomorrow that he’s feeling great, then I’ll play him,” McClendon said. “It has to be he’s feeling great.”