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Encarnacion and Escobar both hit two-run shots in Toronto's highest-scoring inning of the season. The Blue Jays had eight hits in the inning, six of them for extra bases.
Jimenez matched a career high by allowing eight earned runs and was chased after just 2 1/3 innings, his shortest start of the season.
"Everything was wrong today," Jimenez said. "I couldn't get my pitches over the plate. I was falling behind in the count and then once I tried to get in, they took advantage of it. It was a really bad day."
Jimenez (8-8) allowed seven hits, including two homers and four doubles.
"Obviously, Ubaldo didn't have it today," Indians manager Manny Acta said. "He's human. He had seven quality starts in a row for us and he had a bad one today."
Shelley Duncan, Michael Brantley and Casey Kotchman homered for the Indians. Down 10-2 early, Cleveland made it close with a five-run eighth before right fielder Jose Bautista made a nice catch with two on to end the inning.
"I liked the way we ended up making them bring the closer in in the eighth inning," Acta said. "The guys battled and had some good at-bats late in the game. Unfortunately, pitching is the name of the game and we just didn't pitch."
Encarnacion's second homer was a 448-foot solo drive to left-center off Jeremy Accardo in the fifth, a drive that landed in the third-deck restaurant. The home runs were the 24th and 25th of the season for Encarnacion, who signed a three-year, $29 million contract extension over the All-Star break. It was his first multihomer game of the season and the eighth of his career.
"He always had a lot of power and this year he's taking advantage when pitchers fall behind in the count," Jimenez said. "If you make a mistake, he's making you pay for it."
Adam Lind had four hits and drove in four runs for the Blue Jays.
"Just an outstanding offensive day," Blue Jays manager John Farrell said. "It turned out once again we needed every run that was scored."
Aaron Laffey (1-1) worked five innings for his first victory since Sept. 17, 2011, when he beat Toronto while pitching in relief for the New York Yankees. The left-hander allowed four runs and eight hits, walked three and struck out four.
Casey Janssen got the final four outs for his 13th save in 14 chances.
Lind got the Blue Jays started with a two-out, two-run double in the first. Cleveland answered with two in the second when Duncan was hit by a pitch with the bases loaded and Kotchman grounded into a double play.
Bautista doubled to begin the Toronto third and Encarnacion followed with a homer to left. Lind singled and Escobar homered into the second deck in left.
"The potential in this lineup is pretty formidable," Lind said.
J.P. Arencibia chased Jimenez with an RBI double and Brett Lawrie greeted reliever Scott Barnes with a first-pitch double to right. Four batters later, Lind capped the inning by grounding a two-run single.
Duncan started Cleveland's comeback effort with a two-run homer to left in the fourth that made it 10-4.
Trailing 11-4 after Encarnacion's second homer, the Indians fought back against Jesse Chavez in the eighth. Carlos Santana walked and Brantley followed with a two-run shot. Duncan singled and Kotchman chased Chavez by homering.
Rookie Drew Carpenter replaced Chavez and got two outs, then issued back-to-back walks to Asdrubal Cabrera and Jason Kipnis. Janssen came on to face pinch hitter Travis Hafner, who lined an RBI single.
Santana followed with a sinking liner, but Bautista ended the rally with a sliding catch, similar to the one he made to retire Milwaukee's Ryan Braun in Tuesday night's All-Star game.
- Toronto OF Rajai Davis threw out Kipnis at home plate for the final out of the fifth.
- Brantley had three hits, extending his hitting streak to 12 games.
- Indians LHP Rafael Perez (strained back muscle) is scheduled to throw one inning Saturday in a rehab appearance with Double-A Akron.
- The Blue Jays optioned Chavez to Triple-A Las Vegas after the game and recalled RHP Chad Beck from Triple-A.
- Toronto's record for extra base hits in an inning is seven, set Aug. 2, 2010 at New York. On that day, Encarnacion homered and the Blue Jays his six doubles in a seven-run fifth inning, beating the Yankees 8-6.