TORONTO -- The Tampa Bay Rays entered the game with the only undefeated bullpen left in baseball.
John McDonald ended that run.
Tampa blew its first save and suffered its first defeat when McDonald hit a walk-off two-run home run in the 11th inning and the Toronto Blue Jays beat the Rays 6-4 on Friday night.
McDonald connected for his first home run of the season against Rays right-hander Adam Russell (1-1).
"I liked my fastball matchup against him," Russell said. "It just didn't get where I wanted it to go and I paid the price."
Rays relievers came in 3-0 and 4-for-4 in save opportunities but ended up beaten by a light-hitting backup infielder.
"McDonald is our kryptonite," Rays manager Joe Maddon said.
McDonald, who'd never hit a walk-off homer before, said he doesn't relish facing Tampa Bay's staff.
"There's a lot of good pitchers over there," he said. "You don't go into Tampa thinking, 'I can't wait to face [David] Price and [Jeff] Niemann.' But anytime you can make a manager feel that way across the other side it makes you feel like you're accomplishing something."
Marc Rzepczynski (2-0) pitched one-third of an inning for the win as the Blue Jays handed the Rays their second straight defeat.
Toronto's Jose Bautista hit his fifth home run of the season and finished a single shy of the cycle. He went 3-for-3, walked twice and scored four runs.
McDonald didn't start the game, coming on defensively in the second after Blue Jays second baseman Jayson Nix was injured in a knee-on-knee collision with Tampa Bay's Sean Rodriguez, who slid into Nix while trying to break up a double play.
"I didn't think it was a bad slide," Nix said. "I would have done the same thing in the same situation."
Nix left with a sore left knee and is day to day. X-rays were negative.
"I have some pain in the middle of my leg, in the fibula, but the knee is the biggest problem right now," he said.
The Blue Jays are already without regular second baseman Aaron Hill, who missed his second straight game with a sore right hamstring. Hill was injured stealing second in Tuesday's victory over the New York Yankees.
B.J. Upton's sacrifice fly gave the Rays a 1-0 lead in the top of the first, but Toronto tied it in the bottom half. Bautista hit a two-out double that skipped off Sam Fuld's glove in left, sliding into second just ahead of the throw. Adam Lind followed with an RBI single to center.
Fuld singled, stole second and scored on a hit by Upton in the third, but the Blue Jays tied it again in the fourth when Bautista tripled past a diving Ben Zobrist in right and scored on Lind's double.
Needing just a single for the cycle, Bautista walked on four pitches to begin the inning, moving to second on Lind's grounder. Bautista was nearly picked off, staying alive when Rodriguez dropped Peralta's throw.
"I thought it was going to bounce so I kind of picked my glove up just a little bit," Rodriguez said. "I had it snowconed but when I went to turn around it popped out."
Edwin Encarnacion made the Rays pay by lining an RBI double off the right field wall.
Hellickson matched his career high by working seven innings, allowing three runs and six hits. He walked two and struck out six.
Blue Jays left-hander Jo-Jo Reyes gave up four runs and six hits in seven innings. He walked one and struck out six.
Rays left-hander J.P. Howell (left shoulder) threw 25 pitches in an extended spring training game Friday. He struck out four and allowed two hits in 1 1/3 innings. ... Maddon said he would not use Monday's day off to skip Niemann, who is 0-3 with a 7.08 ERA in four starts. ... Toronto outfielder Rajai Davis (right ankle) began a minor league rehab assignment at Double-A New Hampshire on Friday, going 1-for-3 with a strikeout. ... Blue Jays outfielders Scott Podsednik and Dewayne Wise both started for Class A Dunedin in a game at Tampa on Friday night. Podsednik has been bothered by plantar fasciitis. ... The Blue Jays traded infielder Brad Emaus to the Colorado Rockies for right-hander Chris Malone and a player to be named or cash.