The Tigers loaded the bases after Santiago came out in the eighth, but closer Huston Street struck out Yoenis Cespedes to end the inning, then pitched the ninth for a four-out save, his 15th of the season.
"Huston getting four outs is huge," manager Mike Scioscia said. "And it wouldn't have been possible unless Hector got us to a certain point in the game, and he did."
The Tigers managed only three hits against Santiago, who fired 7 1/3 shutout innings and struck out seven. Detroit threatened in the fifth and the seventh, but Santiago kept them off the board both times, including a called strikeout of Nick Castellanos to end the seventh with two on.
"Nothing's really happening. We're scuffling right now offensively," Tigers manager Brad Ausmus said. More >
Anibal Sanchez pitched well for the Tigers, but second baseman Ian Kinsler booted a potential double-play ball with the bases loaded in the fourth, leading to the Angels' first run, and Albert Pujols hit a long home run to left leading off the sixth to cap the scoring.
MOMENTS THAT MATTERED Street gets the extra out: Pitching in the eighth inning for the first time this season, Street got a huge strikeout when he got Cespedes to chase a low slider to escape a bases-loaded, two-out jam. More >
"It's very different," Street said. "The first pitch of the inning could be the critical pitch of the entire game. Whereas you come into a game in the ninth inning with a two-run lead and nobody on base, you can work with a few pitches. It's good, though. It's good to have that feeling."
With normal eighth-inning man Joe Smith unavailable due to a minor neck issue, the Angels first went to Cam Bedrosian, who recorded one out but gave up a single to Rajai Davis and intentionally walked Miguel Cabrera before Street entered the game.
Long ball derails gem: Sanchez bounced back from last Sunday's blown lead with seven strong innings and nine strikeouts over a season-high 117 pitches. With no run support, however, he had no room to make up for Pujols' sixth-inning homer, the 12th off Sanchez this season. More >
"Changeup right in the middle," Sanchez said.
Nieuwenhuis, Trout help out: Santiago pitched a beauty of a game, but it was his outfielders who helped keep the Tigers scoreless. Mike Trout came up with an inning-ending, shoestring catch in the fifth, after the Angels had taken a 1-0 lead in the fourth. With two out, Trout came in at a full run to snare Hernan Perez's soft liner, stranding J.D. Martinez -- who had led off the frame with the Tigers' first hit -- at third base. More >
"Soft, off-the-end-of-the-bat blooper, and you think it's gonna fall in, all of a sudden here comes Trout, just cruising in and doesn't even have to dive," Santiago said. "He just catches it and keeps it coming right to the dugout. It's a great defense right now and they made some great defensive plays tonight."
Then, with Cabrera on first in the seventh, Kirk Nieuwenhuis, making his first start for the Angels in left, made a nice catch at the top of the wall in left-center on Martinez's fly ball.
"I didn't know where the wall was and stuff like that -- it was a little bit tough in a new park," Nieuwenhuis said. "But I'm glad it worked out."
Kinsler's costly error: The Tigers' defense helped out Sanchez with some stellar plays, from Jose Iglesias' highlight throw from deep in the hole to James McCann throwing out Trout trying to steal second. When Kinsler bobbled Matt Joyce's double-play grounder with bases loaded and one out in the fourth, however, the miscue allowed Pujols to score. Sanchez recovered to get another double-play grounder a batter later, but even one run was costly.
Angels setup man Joe Smith was unavailable for Friday night's game after tweaking his neck stretching on Thursday. Scioscia said Smith was receiving treatment, and Smith said he thought the issue was minor, and he was "optimistic" for Saturday.
WHAT'S NEXT Tigers:Shane Greene has never faced the Angels, but he's more focused on his own game at this point after a four-run sixth inning doomed him on Memorial Day in Oakland. He'll try to keep Detroit close and hope for an offensive revival on Saturday night at 10:05 p.m. ET.
Angels:Jered Weaver, who has rebounded from a slow start to the season, takes the mound in the third game of the set on Saturday at 7:05 p.m. PT. Since addressing a mechanical issue -- the righty said he had been jerking his delivery to the side -- he has put together four quality starts in a row.
Jason Beck is a reporter for MLB.com. Read Beck's Blog, follow him on Twitter @beckjason and listen to his podcast. David Adler is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.