Two defensive blunders by the Houston Astros gave Toronto an opening, and the Blue Jays' offense barged right through.
After Astros shortstop Clint Barmes failed to come up with a potential double-play grounder in the sixth, Bautista made Houston pay by swatting a three-run homer.
In the seventh, outfielder Brian Bogusevic came up short on a fly ball from Toronto's Eric Thames. Jose Molina followed with a game-tying single, and Escobar followed with a go-ahead homer.
"That's a tough loss," Bogusevic said. "That's a game we could have won."
Manager Brad Mills said he'd be happy to have any ball hit at Barmes, but the shortstop was inconsolable.
"We've made mistakes a lot of times this year that have hurt us and I made a really big one today," Barmes said. "It's pretty frustrating, that's for sure, especially with what our records reads and how it's gone this year."
Bautista's three-run drive came off Brett Myers in the sixth. He added a solo shot to left against Jose Valdez in the eighth, his third multihomer game of the season and 14th of his career.
"Man, this guy's a freak." Thames said. "You think you can just hold him down, but he makes adjustments. He just smashes the ball."
In the seventh, after Jose Molina tied the game at 4 with a two-out single to center, Escobar hit a two-run drive to left, his fourth.
Escobar's shot also came off Myers (1-4), who has not won since April 12, a span of seven starts. The right-hander allowed six runs, five earned, in 6 2-3 innings. He walked none and struck out two.
"I made some good pitches, but also a couple of mistakes and they hit them hard," Myers said. "Sometimes you get away with them, but I haven't all year. It's been tough."
Casey Janssen (1-0) pitched one inning for the win.
After Jason Frasor worked a perfect eighth, the Blue Jays needed two pitchers to close it out in the ninth. Jon Rauch was replaced after giving up an RBI double to Angel Sanchez. Former Astros closer Octavio Dotel came on and struck out Hunter Pence, then got Carlos Lee to ground out to earn his first save.
The Astros jumped on Blue Jays right-hander Brandon Morrow with two runs in the first. Michael Bourn drew a leadoff walk, Pence hit a one-out single and Houston loaded the bases when Lee reached on a fielder's choice, with Pence beating third baseman John McDonald's throw to second. Brett Wallace drove in the first run with a sacrifice fly and Johnson followed with an RBI single to right, but Lee was thrown out trying to advance to third.
Johnson hit an RBI single in the third and added a sacrifice fly in the fifth as the Astros built a 4-0 lead.
Morrow allowed four runs and nine hits in six-plus innings. He walked three and struck out six.
The Blue Jays struggled to get anything going through the first five innings against Myers, who set down 10 in a row after Bautista's infield single in the first.
Toronto put runners at first and second after a pair of singles in the fifth, but McDonald lined into an inning-ending double play, with Juan Rivera caught off second base.
Molina opened the sixth with a single and Escobar reached on Barmes' error. One out later, Bautista blasted an 0-1 pitch to left, cutting the deficit to one.
Bautista had been struggling to catch up with Myers's fastball, but homered on a hanging curve.
"I know when he has runners on base he throws a lot of offspeed," Bautista said. "Sometimes sliders, sometimes curveballs and sometimes a changeup, but I know his favorite pitch is a curveball. I wasn't sitting on it, but I was looking for something slower."
In the seventh, Thames reached when Bogusevic couldn't get to the rookie's flyball into the gap.
"I had it," Bogusevic said. "At the last second I froze up. I caught a glimpse of (center fielder Bourn) as he was backing me up. I caught a glimpse of him out of the corner of my eye and I froze on it. I should have caught it."
One out later, Thames scored the tying run on Molina's groundball single, and Escobar followed with his tiebreaking homer.
Blue Jays outfielder Corey Patterson went 0 for 4, ending his hitting streak at 11 games.
Notes: Blue Jays 1B Adam Lind (back) was scheduled to hit off the tee at extended spring training on Saturday, his first baseball-related activity since being placed on the 15-day DL. ... Astros INF Jeff Keppinger (left foot) went 1 for 3 with an RBI at Triple-A Oklahoma City on Friday. He's batting .344 (11 for 32) in eight rehab games at Double-A and Triple-A.