CINCINNATI -- Miguel Cairo got the pitch he expected, right where he thought it would be.
Cairo hit a two-run homer in the sixth off Carlos Villanueva, stopping Cincinnati's streak of 16 scoreless innings, and the Reds got their first win over an American League team this season, beating the Toronto Blue Jays 2-1 on Sunday.
The Reds had dropped their previous five interleague games against Cleveland and Toronto.
Bronson Arroyo (6-6) ended his streak of dismal days against the Blue Jays. The right-hander gave up five hits, including Aaron Hill's homer, in a season-high eight innings. Arroyo had lost his last three starts and five straight decisions against Toronto.
"It feels good," Arroyo said. "They've been beating me around pretty good, but that's a totally different lineup."
Villanueva (4-1) lost for the first time since Aug. 17, 2009, with Milwaukee, where he was a reliever the last two years.
Francisco Cordero pitched the ninth for his 15th save in 17 tries. He moved one ahead of Jeff Montgomery for sole possession of 19th on the career list with 305 saves. Hall of Famer Goose Gossage is next at 310.
First baseman Joey Votto had three hits, after failing to reach base in the first two games of a special series. The Toronto native received the Lou Marsh Trophy before Saturday's game honoring him as Canada's top athlete for 2010.
He singled with one out in the sixth and came around on Cairo's homer down the left-field line off a first-pitch fastball that was up and over the inside half of the plate -- not where it was intended.
"It was supposed to go away there," Villanueva said. "If I get it in the away lane, he's not going to hit a home run to the opposite field. We had the right idea, it was just a little bit of a mistake."
Cairo, who was playing third base while Scott Rolen rested for a day, wasn't surprised when the ball came up and in.
"He got me out with a fastball in the last time up," Cairo said, referring to his foulout. "I was looking for a pitch middle-in. I got a pitch and put a good swing on it."
The homer ended a streak of 16 scoreless innings by the NL's most prolific offense. The Reds lost the series opener 3-2, getting a pair of solo homers, and were blanked 4-0 on Saturday.
Villanueva gave up seven hits in seven innings. He ended a streak of 84 outings without a loss.
The Blue Jays have hit Arroyo hard. He gave up a career-high 10 runs while retiring a career-low three batters during a 14-1 loss at Toronto in 2008. A year later, he went back to Toronto and gave up seven runs in 3 2/3 innings of an 8-2 loss.
This time, he had only one shaky inning. Hill led off the fifth with a homer, and the Blue Jays got a runner thrown out at third to scuttle the rally.
"I knew if he bunted that the runner might be off third," Votto said. "They'd tried it earlier in the series, so I had an inkling that they might do it again. It worked out."
The Reds knew it could wind up being the game's pivotal defensive play.
"I told the guys on the bench, 'That's a game-saver right there," manager Dusty Baker said.
During their 4-0 win on Saturday night, Blue Jays outfielder Corey Patterson was tagged out at third after he incorrectly thought the ball had gone out of play, thwarting a rally.
Blue Jays SS Yunel Escobar agreed to a two-year, $10 million contract before the game. He gets $5 million each of the next two years. There are two club options for $5 million as well. ... The Blue Jays go to Atlanta next for three games. The Reds have a three-game home series against the Yankees, making their first visit since 2003. ... Arroyo is 3-5 against Toronto in 12 career starts.