Jose Bautista had hit a two-run homer with no outs in the ninth off Jonathan Papelbon. Then a single by Encarnacion and a walk to J.P. Arencibia put runners at first and second with two outs. John McDonald looped a single that McDonald charged and, on the run, fired the ball on the fly to Jason Varitek.
The catcher tagged Encarnacion to end the game.
Papelbon got his 18th save in 19 chances, while Matt Albers (3-3) picked up the win.
Brett Cecil (1-4) went all the way for Toronto, giving up two runs in the second on an RBI double by Jason Varitek and a run-scoring single by J.D. Drew, and one in the third on Dustin Pedroia's homer.
Boston starter Jon Lester allowed no hits in four innings before leaving with a strained muscle on the left side of his back. Albers worked two scoreless innings and gave up Toronto's first hit, a two-out single by Bautista in the sixth.
Franklin Morales and Daniel Bard each pitched a scoreless inning, but Papelbon gave up a leadoff single to Corey Patterson and Bautista's major league-leading 28th homer of the year.
The Red Sox ended a three-game home losing streak and won for the fifth time in its last six games overall.
They went up 2-0 in the second when David Ortiz led off with a double, took third on a groundout and scored on Varitek's double. Drew then hit a hard shot into the hole between first and second that went off the foot of second baseman Mike McCoy for a single.
Cecil set down the first two batters in the third. Then Pedroia, batting fourth while Kevin Youkilis sat out with a bruised back muscle, drove a 1-2 pitch over the left-field wall for his eighth homer.
Pedroia hit fourth for only the second time this season and homered in each game. He first did it last Thursday when he went 1-for-5 in a 5-2 win over the Philadelphia Phillies. In his six career games batting cleanup, he is 13-for-26 with four homers.
Until the ninth, the Blue Jays got only one runner past first base. After Albers set down the first two batters in the sixth, Patterson walked and took second on Bautista's sharp single in the hole between shortstop and third base. Then Patterson took off for third as Albers was preparing for his next pitch and was caught stealing by the right-hander.
Lester started the game by striking out Rajai Davis, then got Patterson on a groundout before striking out Bautista. He added two strikeouts in the second against Encarnacion and Travis Snider.
Lester then walked Arencibia to start the third but set down the next three batters. He pitched a perfect fourth, ending the inning — and his night — by throwing a called third strike by Adam Lind.
Notes:
Bard has pitched 16 1/3 consecutive scoreless innings. … Bautista has reached base in 74 of his 79 games. … Boston sent OF Mike Cameron and cash to the Florida Marlins for a player to be named or cash. … Toronto's season-high streak of homers reached 13 straight games. … Red Sox LF Carl Crawford, on the disabled list with a strained hamstring, could return before the All-Star break that begins Monday but probably wouldn't play just Sunday, according to manager Terry Francona. … Boston RHP Clay Buchholz planned to fly Wednesday to North Carolina for a second opinion on a lower back strain that put him on the disabled list.