They'll look to become the first club to sweep the Red Sox at Fenway Park all season as they continue their climb toward the final AL wild-card spot on Thursday night.
Trailing Texas by a one game for the second wild-card spot, Baltimore's playoff hopes will likely go down to the wire.
Boston is one win or a Cleveland loss away from its first postseason berth since 2009, and its magic number for its first AL East title since 2007 stands at three after Tampa Bay beat the Rangers on Wednesday.
"We know where the playoffs are. We know how far away we are. We're not stupid,'' Boston catcher David Ross said.
The Red Sox (92-61) had won their last eight series before Chris Davis snapped a 3-for-22 skid with his go-ahead single in the top of the 12th Wednesday to give Baltimore a 5-3 win.
"Any time you're in a game like that you want to be the guy to get the hit - whether it's a squibber up the middle or a home run or whatever it is," Davis said. "You can feel the intensity of both teams trying to get a run. I'll take it whatever way I can get it."
The Orioles (81-70) will give the Red Sox their best shot with Chris Tillman (16-6, 3.70 ERA), who aims to become Baltimore's first 17-game winner since Mike Mussina in 1999.
No pitcher has more wins against Boston since Sept. 28 than Tillman, who has since gone 4-0 with a 1.08 ERA in five starts against the Red Sox. He held Boston to two runs while striking out eight in seven innings of a 3-2 win Aug. 29.
David Ortiz is hitless in 10 at-bats against Tillman. Jarrod Saltalamacchia hasn't been much better, with one hit and six strikeouts in 16 at-bats.
Will Middlebrooks, who snapped an 0-for-17 skid with three hits Wednesday, is 0 for 8 off Tillman.
Only Mike Napoli (.375) and Shane Victorino (.364), who homered off Tillman on Aug. 29, have seen the right-hander particularly well.
Tillman threw a six-hitter in a 4-3 loss in Toronto on Saturday.
"He was solid, just got a couple of changeups up," Orioles manager Buck Showalter said. "It's been a big pitch for him all year. Just elevated a couple and they made him pay for it."
The Red Sox give the ball to John Lackey (9-12, 3.56), who is 1-1 with a 4.35 ERA in three starts against the Orioles this season. He failed to record a decision while giving up three runs in 7 1-3 innings of a 4-3 win over Baltimore on Aug. 28.
He's surrendered five home runs in his last 13 2-3 innings against the Orioles, including two apiece to Manny Machado and Adam Jones.
The right-hander allowed four runs in 6 1-3 innings of an 8-4 win over the New York Yankees on Friday, but didn't record a decision.