Adrian Gonzalez, Kevin Youkilis and Dustin Pedroia also homered for Boston. Youkilis had four RBIs after getting Saturday's 16-4 win off. Gonzalez drove in two runs and Pedroia three for the Red Sox, who never trailed while sweeping the three-game series.
Lester (9-2) kept the Blue Jays off balance all afternoon while winning his league-best ninth game. The ace left-hander walked just one batter and struck out eight while earning his second win in three starts against the Blue Jays this season.
Toronto's Jose Bautista ended a 13-game homerless drought with his 21st of the season in the fourth. Boston's league-leading offense had 17 hits a day after amassing 18.
After scoring seven runs in the fifth inning on Saturday, Boston scored six more in the fifth in the series finale.
The first seven Red Sox in the inning all reached base, the first five against Blue Jays rookie starter Kyle Drabek.
Jacoby Ellsbury singled to start it before Dustin Pedroia homered to extend Boston's lead to 5-1. Gonzalez doubled and Youkilis walked ahead of Ortiz. Big Papi then hit his 17th home run of the season and fourth in six games.
With Ortiz's homer, Drabek was done after four-plus innings. Drabek (4-5) gave up eight runs, seven hits and four walks.
The 23-year-old son of former NL Cy Young winner Doug Drabek threw just 45 of his 91 pitches for strikes as his ERA jumped from 4.98 to 5.70.
Little changed after reliever Luis Perez took over for the Blue Jays. The left-hander, who had not allowed a run in 12 2/3 innings, gave up an RBI single to Marco Scutaro.
Youkilis, Ortiz and Jarrod Saltalamacchia each added RBI doubles off Perez in the sixth that pushed Boston's lead to 12-1.
Gonzalez connected in the first for his 13th home run. The American League RBI leader has driven in at least one run in nine consecutive games, extending his new career-high and setting a new season-best mark for the AL.
Gonzalez also had an RBI groundout.
Youkilis capped the scoring with his ninth home run of the season, off Blue Jays closer Jon Rauch.
Lester retired the first 11 batters he faced before Bautista trimmed Boston's lead to 3-1 with his 21st home run of the season.
Notes:
Red Sox manager Terry Francona sat Jed Lowrie on Sunday and said the shortstop could get another day off to help his sore right shoulder heal. … Ortiz interrupted Francona's morning meeting with the media to give the manager a pair of Boston Bruins hats to try on. The Bruins are playing in the NHL's Stanley Cup Final against the Vancouver Canucks. … According to the Elias Sports Bureau, Gonzalez's nine-game RBI streak is the second longest in team history behind only Dwight Evans' 10-game run from Sept. 15-26, 1989. … The Baltimore Orioles announced Chris Jakubauskas will start Tuesday's opener of their three-game series at Toronto. … Ellsbury's fifth-inning singled extended his hitting streak to 10 games. … Boston's nine-game winning streak is the franchise's longest since an 11-game run Apr. 15-27, 2009.