Lyle Overbay's solo homer in the sixth inning was the difference as the Blue Jays averted a sweep by the Angels with Thursday night's 4-3 victory in front of 22,007 at Rogers Centre.
While catcher Jeff Mathis was second-guessing himself for putting down the wrong fingers on the 2-2 delivery that decided it, Santana was shouldering the blame for the execution.
"That was right in the middle [of the plate]," Santana said. "I was trying to bounce it, but I didn't finish the pitch.
"The only thing I control is to throw to him [the catcher] and throw strikes. After that, nothing else. This was a great game ... except for that one pitch."
Overbay had seen a number of sliders, but he was ready for this one.
"With two strikes, he's been burying a few of them," the first baseman said. "He ended up leaving a slider in, and I actually put a good swing on it for once."
While Santana endured his third start without a victory after claiming wins in six in his first seven outings, A.J. Burnett (5-4) prevailed with sterling support from southpaws Jesse Carlson, Scott Downs and B.J. Ryan.
The relievers faced the minimum from the seventh through the ninth, with Garret Anderson's second infield hit of the night erased by a double-play grounder by Torii Hunter in the eighth.
"We lost the last one," the eternally upbeat Hunter said, "but two out of three is good. Ain't all peaches and cream every day. You know baseball -- it's a humbling experience."
Burnett, who has humbled a lot of hitters with a mid-90s fastball complemented by a wicked hook, made Hunter a strikeout victim twice with curveballs before walking him in the sixth with two outs.
Mathis' line-drive single to center on a two-strike, 94-mph heater cashed in Hunter to tie it after Casey Kotchman's second single had moved Hunter to third.
"He's got some of the best stuff I've seen as far as a fastball being electric and his breaking stuff being sharp," Mathis said. "When he's throwing it for a combo, he's tough to beat."
Burnett retired Brandon Wood -- on his first day back with the varsity -- to quell that threat, and the Angels were about to be dismissed by the Jays bullpen. Carlson struck out the side in the seventh, and Ryan finished it by striking out dangerous Mike Napoli in a pinch-hitting role.
"We won a couple ballgames," Angels manager Mike Scioscia said, "but tonight we couldn't get going offensively."
Chone Figgins, the Angels' leadoff catalyst, sat out after showing up with soreness in his right leg. Figgins made his return Wednesday night from the disabled list and hopes to be back in the lineup in Chicago, where the Angels kick off a three-game weekend series Friday night against the White Sox.
Santana took this start a day ahead of his scheduled outing when Joe Saunders turned up ill and was pushed back. The lefty will pitch Friday night, assuming he's over the congestion that led to headaches and a lack of energy.
Scioscia maintained that there was nothing at all wrong with Santana, that his stuff and his delivery were the same caliber as during his winning run.
Dealing 95-mph heaters around biting sliders and changeups, Santana struck out seven, one more than Burnett's six.
The Jays struck first in the third when Marco Scutaro doubled and scored on a triple by designated hitter Joe Inglett, who was promptly singled home by Brad Wilkerson.
The Jays made it 3-0 in the fourth on three singles and a walk, with Rod Barajas driving in the run, before Santana escaped a bases-jammed, one-out situation.
Barajas' hit, like Shannon Stewart's in front of him, was a flare that eluded a charging Vladimir Guerrero in right field.
"A couple of bloopers," Santana said, shrugging. "You can't do anything about that."
Anderson and Hunter threw perfect strikes from the outfield behind Santana to erase runners trying to stretch singles. Anderson nailed Scott Rolen in the second inning, and Hunter erased Wilkerson in the third on his RBI hit to right-center.
"Our defense and pitching are getting it done for us," Hunter said. "We have to come alive offensively -- and we will."
The Angels broke through against Burnett in the fifth. Kotchman singled, Mathis was hit by a pitch and slump-ridden Sean Rodriguez -- who played superior defense at second throughout the series -- stroked a two-out, two-strike RBI double to left, driving in his first run in the Majors.
"That was a great at-bat," Scioscia said of Rodriguez's blow. "Mentally, he's a tough kid."
Izturis followed that with an opposite-field double over the head of Stewart in left, cashing in Rodriguez.
When the Angels drew even in the sixth on Mathis' bullet, the catcher felt renewed. His bat had been in hibernation for a spell.
"Yeah, that felt good to hit something solid in that situation," Mathis said. "But then I called a pitch I'd like to have back."
Asked what he should have ordered from Santana instead of the slider to Overbay, Mathis shook his head.
"Something else," he said. "Anything else."
Lyle Spencer is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.