The Yankees tried to rally in the ninth, opening the inning with consecutive singles before Jeremy Accardo struck out Rodriguez and retired Jason Giambi on a deep fly. Robinson Cano flied out to end it.
Alex Rios hit a pair of RBI singles and scored once, sending Toronto to its first win of 2007. The night before, New York won 3-2 in the 84th and final opener at storied Yankee Stadium, a game that was postponed Monday because of rain.
Wednesday was dry in the Big Apple, but windy and raw. The gametime temperature was 44 degrees, and a sign posted on Mussina's locker in the late afternoon read: "Toronto vs. New York at Lambeau Field. Windchill - 6 degrees."
The cold weather must have made it uncomfortable for batters facing Burnett (1-0), who was throwing 96 mph fastballs and a steady diet of strikes.
He's given the Yankees trouble before, too. Burnett was 1-0 with a 0.60 ERA in two starts against New York last year, allowing one run over 15 innings. He won 6-0 at Yankee Stadium on April 26.
Burnett had a 7.36 ERA in spring training, though he couldn't throw his curveball until late March because of a broken nail on his index finger.
Brian Tallet relieved Burnett and struck out three in two perfect innings. Accardo, filling in for injured closer B.J. Ryan (elbow surgery) as he did last year, got the save.
Wells finished with three hits and Aaron Hill added an RBI single for the Blue Jays, who grounded into five double plays. Still, they chased Mussina (0-1) in the sixth after 91 pitches.
The 39-year-old right-hander is coming off an inconsistent season that included him temporarily losing his spot in the rotation before he finished 3-0 with a 2.73 ERA in September.
Pushed up to pitch the second game of the year because of Andy Pettitte's back spasms, Mussina gave up four runs - three earned - and eight hits in 5 2-3 innings.
He remained at 250 wins, one behind Hall of Famer Bob Gibson on the career list.
A two-time All-Star, Wells had a subpar 2007 season that ended with shoulder surgery in September. He looked healthy Wednesday night, connecting off Mussina in the third with Rios aboard on a two-out walk.
Mussina nearly struck out Rios moments before, but didn't get a close call from plate umpire Jerry Meals.
A trainer came out to check on a hobbling Burnett after his throwing error on Derek Jeter's fourth-inning comebacker. Burnett, however, threw two warmup pitches and stayed in the game.