The AL East leaders, who had a seven-game winning streak snapped Friday, have won 15 of 19 on the road.
Toronto dropped to 4-11 against New York this season and has lost 18 of 24 overall.
After flirting with a perfect game in his previous outing against Baltimore, Pettitte (13-6) allowed four runs and four hits in six innings. The left-hander, unbeaten in eight starts, walked five and struck out three.
David Robertson worked the seventh, Brian Bruney got two outs in the eighth and Phil Hughes closed it out for his third save.
All-Star closer Mariano Rivera threw a bullpen session before the game and reported no pain in his sore left groin, meaning he might be able to return to the mound Sunday.
Derek Jeter returned to the lineup after a day off and got two hits, leaving him seven shy of breaking the Yankees record held by Lou Gehrig (2,721).
Cano hit a leadoff homer to right in the fourth, his 23rd, and Teixeira led off the fifth with a shot to left, his team-leading 33rd.
Both homers came off rookie left-hander Brett Cecil (6-4), who allowed three runs and seven hits in 4 2-3 innings while losing for the third time in four starts. Cecil walked three and struck out four.
Pettitte retired his first 20 batters Monday night at Baltimore before an error by third baseman Jerry Hairston Jr. ended his bid for perfection. Pettitte gave up a single to his next batter, Nick Markakis.
This time, Pettitte walked leadoff hitter Marco Scutaro in the first inning.
Leading 1-0 on Melky Cabrera's RBI single in the second, Pettitte appeared to give up his first hit in the bottom half when rookie Randy Ruiz hooked a 1-0 pitch down the line in left.
Third base umpire Jeff Nelson ruled it a home run but, after Ruiz circled the bases, the umpires huddled near third base before three jogged off the field and under the first-base stands to watch a replay, the first video review at Rogers Centre.
After about 5 minutes, they emerged and waved Ruiz back into the batter's box. Television replays indicated that the ball was indeed foul.
Ruiz ended up grounding to third but homered to left-center in his next at-bat.
Pettitte walked the next two batters before John McDonald dropped a single into short right that rolled past a charging Eric Hinske, scoring Edwin Encarnacion. Cano retrieved the ball and fired it to the plate in time to nail Jose Bautista, who was trying to score from first. Bautista appeared to slide home ahead of the tag from catcher Jorge Posada but was called out by plate umpire Tim Tschida.
Leading 3-2 on Teixeira's homer, New York added two more in the sixth off reliever Casey Janssen on RBI singles from Alex Rodriguez and Posada.
Toronto cut it to 5-4 in the bottom half. Bautista tripled home Encarnacion and scored when Jeter's errant relay throw bounced away and was picked up by a fan.
Cabrera gave New York some insurance with an RBI single off Jason Frasor in the ninth.
Notes
New York purchased the contract of RHP Josh Towers from Triple-A Scranton/Wilkes-Barre and released C Kevin Cash to make room on the 40-man roster. … RHP Ian Kennedy threw batting practice at New York's spring training site in Tampa, Fla., for the second time since undergoing surgery in May for an aneurysm below his right biceps. Kennedy might be ready to pitch a simulated game next week. … Posada and Rodriguez are expected to get the day off Sunday. … Encarnacion was activated from the 15-day disabled list before the game. … McDonald made his first career start in left field.