Santiago, acquired as part of the three-team trade that sent Mark Trumbo to the D-backs in December, pitched around two Angels misplays and his own two walks to allow only a first-inning run, giving up one hit and striking out three in a 49-pitch outing.
"Little erratic in the first 15, 20 pitches, but after that I was able to settle down," Santiago said. "That's just more adrenaline, just getting out there and competing against hitters with an umpire back there and getting in a game situation."
Seven regulars were in the A's lineup: Coco Crisp, Lowrie, Donaldson, Brandon Moss, Stephen Vogt, Eric Sogard and Cespedes. Crisp went 0-for-3 with two strikeouts, Lowrie scored two runs and Moss worked two walks. Outfielders Michael Taylor and Sam Fuld, both competing for a spot off the bench, went hitless.
The Angels also had seven regulars in their lineup: Erick Aybar, Mike Trout, Albert Pujols, David Freese, Howie Kendrick, Chris Iannetta and Ibanez. Aybar reached base twice with a single and a walk, and outfielder Brennan Boesch -- competing for a bench spot after signing a Minor League contract -- notched two singles.
Facing lefty Joe Savery with one out in the fifth, Trout drew a walk to load the bases, but Pujols grounded into a 5-3 double play to end the inning and cap an 0-for-3 day.
Right-hander Jesse Chavez, competing for a spot in the A's bullpen, pitched 2 2/3 scoreless innings to start the game, giving up one hit and one walk while striking out two. Reliever Dan Otero pitched a 1-2-3 sixth, then allowed two hits and struck out two in the seventh before exiting.
Up next: Garrett Richards, the 25-year-old right-hander who has a set rotation spot for the first time in his career, makes his first start of the spring when the Angels take on the D-backs in Scottsdale, Ariz., on Monday. Richards secured his spot after posting a 3.72 ERA in 13 starts down the stretch last season. Closer Ernesto Frieri is slated to make his spring debut after his wife gave birth to the couple's second daughter Friday in Phoenix. The game starts at 12:10 p.m. PT and can be seen on MLB.TV, or as a simulcast between FOX Sports 1 and FOX Sports West.