Edwin Encarnacion had a two-run shot and rookie Eric Thames also connected for the Blue Jays in the eighth to chase Lee.
The Blue Jays also hit three homers in an inning on April 25 victory at Texas.
Octavio Dotel (2-1) pitched 1 2-3 innings for the win and Rajai Davis went 3 for 4 with three stolen bases for Toronto, who had lost five of six.
Lee (9-6) gave up a season-high seven runs - six earned - and 10 hits in 7 1-3 innings. He walked none and struck out nine.
The left-hander, who went 5-0 with an 0.21 ERA in five June starts, had not lost since May 31 at Washington and came in having pitched three consecutive shutouts. He extended his scoreless innings streak to 34 before giving up a run in the third.
Lee's scoreless innings streak is the second longest in Phillies history. Grover Cleveland Alexander threw 41 consecutive shutout innings in 1911.
The Phillies jumped on Blue Jays left-hander Jo-Jo Reyes with a four-run second. Shane Victorino doubled and scored on Ben Francisco's single, Domonic Brown singled and Carlos Ruiz drove in Francisco with a ground-rule double to right-center. One out later, Jimmy Rollins capped the rally with a two-run single to right.
Toronto scored the first run against Lee since June 11 when Davis tripled to lead off the third and came home on John McDonald's grounder to shortstop.
Davis was involved again as the Blue Jays made it 4-2 in the fifth, reaching on a single and stealing second and third before scoring on a two-out hit by Aaron Hill.
For Davis, the stolen bases were his first since June 4.
The Blue Jays cut it to one run with an unearned run in the sixth. Bautista singled and went to third when Francisco made an error on Lind's bloop single down the line in left. Juan Rivera followed with a sacrifice fly to center, with Victorino stumbling and falling as he tried to throw to the plate.
Victorino stayed down and appeared to have twisted his left ankle on the play. He was tended to by trainers and remained in the game.
A baserunning error by Victorino cost the Phillies an insurance run in the eighth. Reliever Marc Rzepczynski left after Victorino's double to right and Philadelphia sent pinch hitter Raul Ibanez to the plate to face Dotel. After Victorino was caught in a rundown between second and third, Ibanez doubled to left but was stranded when Brown flied out to end the inning.
Thames immediately made the Phillies pay by crushing a leadoff drive to center in the bottom half his third. Bautista followed with a towering drive to left off fellow All-Star, the fifth time this season the Blue Jays have hit back-to-back homers.
Adam Lind singled and Rivera flied out before Encarnacion chased Lee with a two-run blast into the second deck in left-center, his sixth.
NOTES: Blue Jays SS Yunel Escobar missed his second straight game. Escobar left in the first inning of Friday's game after being hit on the left hand by a pitch. ... Bautista, the leading vote-getter in All-Star game history, thanked fans in a recorded message played on the scoreboard. Bautista received 7,454,753 votes.