Baltimore wanted Guthrie to go deep into the game and give its depleted bullpen a rest on this humid evening. He tossed 7 1/3 strong innings, but longtime Orioles nemesis Jon Lester helped hand the host team its 10th straight loss as Boston broke open the game late for an 8-2 victory before 40,001 at Camden Yards.
Guthrie and Lester battled through six scoreless innings before Youkilis lined a homer to left on the first pitch of the seventh. Then, in the eighth, Josh Reddick tripled on the first pitch of that inning and scored on Marco Scutaro's one-out single for a two-run lead.
Guthrie (3-6) gave up just those two runs on five hits. His ERA fell to 3.71 after he did just what interim manager Juan Samuel wanted -- but the offense didn't give him much help.
"We got what we wanted out of Guthrie," Samuel said. "He threw the ball very well. He did a tremendous job, went deep in the game for us after using most of the bullpen last night."
The Orioles (15-41) were so concerned about their bullpen that they moved Brad Bergesen there before the game and even scratched starter Jake Arrieta from his start at Triple-A Norfolk to, as Samuel put it, "give us some flexibility."
Guthrie threw 95 pitches and stayed in command throughout. He avoided trouble in the sixth, when Scutaro hit a ball into the left-field seats that the umpires initially ruled foul before reviewing it and upholding the call.
It was the first review at Camden Yards this year and the third overall.
"It is always a very tough lineup," Guthrie said. "They always work the count, so it was nice to get deep into the game like that. I didn't have too many three-ball counts, a few, but I got bailed out a couple of times by some aggressive hitters."
The Orioles were aggressive themselves against Lester but came up with nothing. Lester gave up just four hits in 6 1/3 shutout innings to improve to 7-2.
Lester now has an 11-0 career record against the Orioles.
"[Lester was] tremendous," said Boston manager Terry Francona. "Going into his last inning of work, not giving up any runs, I thought I went one hitter too far with him. He sort of hit a wall."
The Orioles staged a few threats against Lester but came up empty each time. They had runners on second and third with one out in the fifth, but Lester got Cesar Izturis to pop to third and Corey Patterson to ground out.
Baltimore loaded the bases with three straight one-out walks in the seventh, a sequence that ended Lester's night. But Daniel Bard came on to retire pinch-hitter Luke Scott and Patterson to keep Boston (32-24) in front, 2-0.
"I think if we scored some runs in that inning when we had the bases loaded and the right guys up there, I think it was a different ballgame," Samuel said.
The Red Sox broke it open with a six-run ninth inning. Pinch-hitter Darnell McDonald and Bill Hall hit back-to-back two-run doubles off Will Ohman. Youkilis later completed his three-RBI night with the inning's third two-run double, a shot to left off Jason Berken.
"Jeremy pitched a great game, Dave [Hernandez] came in and got some big outs," Ohman said. "I didn't pick him up. I gave them the momentum."
The Orioles snapped a string of 20 scoreless innings when Scott Moore hit a two-run single in the ninth. But that's the only offense they've gotten so far in this series. It's why Guthrie's good pitching went for naught.
"It's a long season, so you cannot control things," Samuel said. "I'm sure if we were winning some more games, those breaks [would] come our way. It's just unfortunate that we have to dig ourselves out of it, keep fighting. It's going to change."
Jeff Seidel is a contributor to MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.