Before tonight, left-handers were batting .302 this season against Orioles starter Bud Norris.
Brandon Moss, a left-handed hitter, delivered an RBI single in the first inning and homered to right field in the third to give Oakland a 3-0 lead.
Moss' home run came with two outs. Coco Crisp, a switch-hitter, led off the inning with a home run to right.
Norris struck out the side in the third, but he won't remember the inning fondly.
Crisp pulled a slider onto the flag court. Moss hit a changeup.
Norris allowed two home runs in his Orioles debut, and none in his next three starts.
Also before tonight, opponents were swinging at first pitches from Norris 31.8 percent of the time, the highest rate in the American League - just ahead of Oakland's Jarrod Parker (31.2 percent), who starts on Saturday.
Crisp swung at the first pitch in the third and circled the bases, making him 3-for-8 with two homers lifetime against Norris.
Crisp also scored in the first inning by reaching on a leadoff single, moving to second on Jed Lowrie's sacrifice bunt and coming home on Moss' two-out single off the glove of Orioles first baseman Chris Davis.
Norris has allowed 18 runs in the first inning, his second-highest total. He's given up 23 in the fourth.
In three career starts against the A's before tonight, Norris is 0-2 with a 7.82 ERA in 12 2/3 innings.
Athletics starter Dan Straily walked a career-high five batters last season in his only start against the Orioles. He issued walks to two of the first three batters he faced in the first inning tonight, but both runners were stranded.
Update: Adam Jones gave the Orioles their first hit of the game, and it was a two-run homer in the bottom of the fourth inning that reduced the A's lead to 3-2.
Davis walked and Jones cleared the out-of-town scoreboard in right for his 27th homer. He has 93 RBIs.
Straily threw two sliders, a fastball and another slider that Jones took to the opposite field.
The Orioles weren't done. Matt Wieters singled, Nick Markakis walked and Ryan Flaherty singled to load the bases with one out. Brian Roberts followed with his sixth career grand slam, and his first since Sept. 12, 2009 off the Yankees' A.J. Burnett.
Orioles 6, A's 3.
Wieters, Davis and Nate McLouth also have grand slams this season.
Straily was removed after Roberts blast onto the flag court. The Orioles sent 10 batters to the plate in the fourth.
Norris has seven strikeouts in four innings, one short of his season high, which came in his debut with the Orioles.