Litsch gave up three runs in the first three innings, then held the Angels scoreless as he pitched into the seventh inning of a 5-4 victory Thursday night, Toronto's 24th in 35 games against Los Angeles.
The Angels also lost two of three at Toronto on Aug. 14-16, and have dropped four consecutive season series against the Blue Jays dating to 2003.
"We had some chances early, then (Litsch) put up some zeros and they held the lead," Angels manager Mike Scioscia said after the loss trimmed Los Angeles' AL West lead over Seattle to one game.
Litsch (5-6) allowed three runs, two earned, on six hits in 6 1/3 innings. Jeremy Accardo ran his string of scoreless appearances to 10 games and 10 innings by pitching a 1-2-3 ninth. The save was his 25th in 29 chances.
"(Litsch) struggled early on with his location. He was leaving some balls up and they hit him around, but he hung tough," Toronto manager John Gibbons said.
"He found a little groove and rolled it through a couple of innings to get us later into the game. It's never easy against them because they've got some pretty good hitters in that lineup. But Accardo did it again."
Litsch had to battle in the early innings, and got out of the fourth unscathed by striking out Orlando Cabrera with the bases loaded.
"I was missing spots a little bit, so I just tried to work in and out a little more and try to keep hitters more off-balance than I was doing," he said.
The Angels' Vladimir Guerrero hit a pair of solo homers, the first off Litsch in the third inning and the second off Casey Janssen in the eighth, after driving in Los Angeles' initial run with an RBI groundout in the first inning.
Litsch said neither he nor Janssen threw bad pitches on Guerrero's homers.
"Mine just flattened out a little bit and he got all over it. Casey's was down and away, where he wanted it, but Guerrero's a good hitter," Litsch said.
Santana (5-12) gave up five runs and eight hits with one walk in six innings. He struck out four in his second start since being recalled from the minors.
"It wasn't an awful start and he made some good pitches," Scioscia said. "But he needed to close out innings."
Santana held Boston to one run over 6 1/3 innings last Friday, but got no decision in the Angels' 7-5 victory.
He said after the loss to Toronto that he felt he was throwing about the same as he did against the Red Sox.
"My confidence is as high as it's been in a long time," Santana said through a translator. "They adjusted against me more than I did against them. I've got to give them the credit."
After falling behind 3-0, the Blue Jays scored twice in the fourth inning after Santana retired the first two batters. Toronto then took a 5-3 lead in the third.
Stairs' two-run double put Toronto ahead, and they scored their fifth run when he went to third on a wild pitch by Santana, then continued home when rookie catcher Ryan Budde's throw sailed high over the head of third baseman Maicer Izturis for an error.
Vernon Wells' RBI double and a run-scoring single by Frank Thomas accounted for the Blue Jays' runs in the fourth inning.
Guerrero's home runs, his 20th and 21st, ended his stretch of 18 games without homering. He hadn't hit one in Anaheim since June 23.
- Toronto 3B Troy Glaus still hasn't had a hit against his former teammates in Anaheim. He went 0-for-9 in five games against the Angels last year when he first came back to town, and went 0-for-4 with two strikeouts in Thursday's series opener.
- Los Angeles 1B Casey Kotchman is listed as day-to-day with a bruised left thumb and strained left middle finger, both hurt while he was pinch-hitting during Wednesday's 8-2 loss to the Yankees.