Edwin Encarnacion and Eric Thames hit back-to-back home runs, Carlos Villanueva won for the first time in five starts and the Toronto Blue Jays beat the Orioles 8-5 on Thursday night, handing them their eighth consecutive series loss.
"It's unfortunate," Orioles outfielder Adam Jones said. "We started out on top and couldn't maintain it."
Baltimore has not won a series since taking two of three against Cincinnati from June 24-26.
Hardy homered to left on Villanueva's second pitch of the game, his 17th and the fourth time this season he's led off a game with a home run.
Two outs later, Guerrero whacked a drive to left, his eighth.
"Not the way I wanted to start off," Villanueva said.
Toronto tied it in the bottom of the first against Brad Bergesen. The Blue Jays loaded the bases with a double, a walk and an error by first baseman Derrek Lee before Encarnacion drew a bases-loaded walk and Thames followed with a sacrifice fly.
"At this level, momentum is everything," Bergesen said. "We had it in our favor and I gave it right back."
Encarnacion went 3 for 4 with two RBIs and scored twice for the Blue Jays, who have won 27 of 31 home games against Baltimore dating to 2008.
Acquired from St. Louis on Wednesday, outfielder Colby Rasmus made his Blue Jays debut, starting in center field and batting second. He went 0 for 5 with two strikeouts and was the only Toronto starter not to reach base.
"With all the stuff going on, my mind was all over the place," Rasmus said. "I couldn't relax and settle down, my mind was everywhere."
Villanueva (6-2) had not won since beating St. Louis on June 25. He allowed four runs and six hits in five innings, walked two and struck out one.
Four of Hardy's five hits in the series were home runs.
"It's good to see J.J. Hardy leave," Toronto manager John Farrell said. "He had a heck of a series."
The Blue Jays took the lead for good and chased Bergesen with a four-run third, doing all the damage with two outs. Encarnacion homered to left, his eighth, and Thames followed with a drive to right, his fifth. It was the sixth time this season the Blue Jays went back-to-back.
"It's disappointing," Orioles manager Buck Showalter said. "We've got an 0-2 count, two outs and nobody on. Next thing you know he's given up some runs that were a dagger for us."
Aaron Hill walked and went to third on Travis Snider's single, sliding in safely when third baseman Mark Reynolds dropped the throw. Both runners scored when J.P. Arencibia followed with a double down the left-field line, with Snider safe at the plate when Matt Wieters fumbled the relay from Reynolds.
Showalter called the missed catches "two sure outs we should have had."
Bergesen (2-7) allowed six runs, four earned, and six hits in three innings, his shortest outing of the season. He walked three and struck out none.
"I didn't slow the game down when I needed to," Bergesen said. "I just kept going quicker and quicker with my tempo."
Baltimore cut it to 6-4 in the fifth on a two-run single by Jones, but the Blue Jays answered with two in the bottom half against reliever Mark Hendrickson. Encarnacion scored from third when Reynolds couldn't handle a pickoff throw from Wieters, and Yunel Escobar followed with an RBI single.
Hardy hit a two-out homer in the ninth, his 18th. It was his second multihomer game of the series and the sixth of his career.
LHP Brad Mills will start for Toronto against Texas on Saturday. He takes the spot of LHP Jo-Jo Reyes, who was designated for assignment last week. ... The Blue Jays optioned INF Mike McCoy to Triple-A Las Vegas to make room on the roster for Rasmus, utilityman Mark Teahen, LHP Trever Miller and Walters. Walters was optioned to Las Vegas after the game, with RHP Jesse Litsch recalled in his place. ... INF Cesar Izturis (right elbow) will work out with the Orioles when they open a four-game series in New York on Friday, but Showalter isn't sure when he will be ready to come off the 60-day DL. ... Orioles RHP Koji Uehara extended his scoreless innings streak to 14 with one shutout frame and has not allowed a run since June 19 at Washington.