Santana, who warmed up in the bullpen the previous night as the Angels played the third-longest game in team history, won on the road for the first time this season as Los Angeles defeated New York 4-1 Friday night.
"Last night he was going to pitch, within reason, until somebody won or lost it," manager Mike Scioscia said after the Angels snapped a four-game skid to avoid their longest losing streak of the season.
Scioscia said he hadn't come so close to using the next day's starter in at least five years.
The Angels were prepared to call up an emergency starter from their farm system if they had needed to replace Santana, but Toronto's victory in the 18th inning of the 4-hour, 50-minute game negated that possibility.
Changing speeds as he mixed his fastball and curve, Santana (6-4) allowed six hits in 6 1/3 innings to help shrink a road ERA that was 14.63 when the night began.
The late finish in Toronto kept the Angels from arriving in New York until 4 a.m., but Santana said it was akin to what happens all the time in the minor leagues, which is where he was pitching when this season began.
Santana said he merely got loose in the Toronto bullpen and only threw a couple warmup pitches at full speed.
"I was keeping the chart all game, and when I was told to go to the bullpen, I just went," Santana said through a translator. "I was basically ready to go into the game, but fortunately I didn't have to and was able to pitch well tonight."
There certainly was plenty of life left in the 22-year-old's right arm.
Santana allowed two walks, hit two batters and struck out five. He breezed through the first five innings before getting a little wild in the sixth.
Hideki Matsui was hit on his back leg by a first-pitch fastball, and Jason Giambi drew a walk to bring the potential tying run to the plate. Jorge Posada fouled off three two-strike pitches before hitting a fly ball off the end of his bat to right field, where Juan Rivera made a diving catch for the final out.
In the seventh, Tino Martinez led off by hitting Santana's 97th pitch into the right-field bleachers to make it 3-1. That prompted Scioscia to start warming up his bullpen, and right-hander Brendan Donnelly got the call after Derek Jeter hit a one-out double to right.
Garret Anderson hit a two-run homer and Bengie Molina added a solo shot in the second inning, giving the Angels all the runs they needed to defeat the Yankees for the sixth time in eight meetings this season.
Los Angeles scored three times in the second inning against Mike Mussina (10-6).
Anderson turned on a fastball and yanked a line-drive homer into the upper deck in right field with a man on. Two outs later, Molina turned on an inside pitch at the knees and pulled it 12 rows deep into the seats in left for a 3-0 lead.
"One bad inning, that was it," Mussina said. "Just a couple of bad (pitches), in fact. I didn't make a lot of mistakes, but the ones I did make, they got me."
- The Yankees drew their 13th consecutive sellout crowd, passing 2.5 million fans for the season.
- Molina's home run snapped an 0-for-19 slump.
- Shawn Chacon, acquired Thursday from Colorado, will be New York's 10th starting pitcher this month and 13th this season when he takes the mound Saturday. "It's an opportunity for me to try to come in and run with it," Chacon said. "(Leaving Colorado) is probably going to be a pretty good thing for me. I've never seen a pitcher leave Coors Field and become a worse pitcher." Chacon is 2-20 since making the NL All-Star team in 2003. He'll be the 24th pitcher the Yankees have used this season.
- Pitcher Kevin Brown visited a back specialist in Los Angeles who confirmed the diagnosis of a lumbar strain made by Yankees team doctor Stuart Hershon. Brown will be re-evaluated in two weeks.
- Giambi is in an 0-for-11 slump.