The right-hander looks to continue a strong stretch at Angel Stadium on Wednesday night, while Anaheim native Chris Tillman will try to lead the Baltimore Orioles to their first road sweep since early May.
The AL East-leading Orioles (55-44) have a major league-best 122 home runs, and they've used the long ball and solid pitching to claim back-to-back 4-2 victories in the first two of this three-game set.
After Adam Jones homered twice Monday, Jonathan Schoop's two-run shot broke things open Tuesday as the Angels lost two straight for the first time since June 15-16.
Now the Orioles can earn their first sweep in Anaheim since August 2010, though they could be without Manny Machado for a second straight contest due to lower back stiffness.
"It's still a little tight, but I got a shot and we'll see where we are tomorrow," Machado said.
Even if Machado is able to go, Baltimore faces a difficult challenge against Weaver (10-6, 3.43 ERA), who has gone 3-0 with a 2.78 ERA while allowing just two home runs over his last six outings - all Los Angeles victories. He gave up two runs over six-plus innings in Friday's 3-2, 16-inning home win over Seattle.
Weaver is 5-2 with a 2.26 ERA in his last 10 starts at home, where the Angels (59-40) haven't been swept since opening the season with three straight losses to the Mariners.
He's gone 6-4 with a 3.06 ERA in 10 career starts versus Baltimore. He had a four-start winning streak against the Orioles snapped on June 10, 2013, when he allowed four runs over 5 2-3 innings in a 4-3 road loss.
Jones homered off him in that contest and is 5 for 16 with four RBIs in the matchup. His last four hits in 18 at-bats over his past five against the Angels have been homers.
Fellow All-Star Nelson Cruz - second in the majors with 28 home runs - is hitting .227 with two homers and 20 strikeouts in 66 career at-bats in the matchup.
The Orioles turn to Tillman (7-5, 4.03) as they seek their first road sweep since taking three in Tampa Bay from May 6-8. He's 6-0 despite a 4.96 ERA in 12 road starts, though he's allowed just four runs over 20 2-3 innings in his last three.
The right-hander gave up two runs over 6 2-3 innings Friday before the bullpen blew his lead in the ninth of a 5-4 loss at Oakland. He's allowed three earned runs or fewer in eight straight outings.
Tillman, who starred at Fountain Valley High School in Orange County, is 2-0 with a 1.84 ERA in two career starts against the Angels. In his only outing in Anaheim, he surrendered three hits over eight shutout innings in a 5-1 win May 2, 2013.
He'll have to be careful with All-Star MVP Mike Trout, who is batting .357 with four home runs and 12 RBIs in his last nine games after hitting his 24th homer Tuesday.
The Angels lead the majors with 5.0 runs per game, but they've totaled 12 and hit .184 with runners in scoring position while dropping three of four.
"You're not going to square it up every night, and you're not going to find a hole every night," manager Mike Scioscia said. "We certainly haven't the last couple of nights."
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