Jon Lester (7-2) gave up four hits and three walks in 6 1/3 innings to win his seventh straight decision, matching the longest unbeaten run of his career. The left-hander is 11-0 with a 2.06 ERA lifetime against the Orioles.
Jeremy Guthrie (3-6) was nearly as effective for Baltimore. But after allowing only two hits through six innings, his first pitch of the seventh inning was driven by Youkilis into the left-field seats.
Boston added a run against Guthrie in the eighth when newcomer Josh Reddick tripled and scored on a single by Marco Scutaro.
The Red Sox broke it open in the ninth, using two-run doubles by pinch-hitter Darnell McDonald, Bill Hall and Youkilis to go up 8-0.
Baltimore ended a run of 19 straight scoreless innings in the bottom half when Scott Moore hit a two-run double, but that was perhaps the lone flaw in Boston's seventh straight road win — its longest such run since June 2005.
The punchless Orioles have been outscored 19-2 in two games under interim manager Juan Samuel. Baltimore has scored only 16 runs during its season-high 10-game skid, including 10 over the last eight games.
Baltimore threatened in the seventh, when Lester walked the bases loaded with one out. But Daniel Bard retired pinch-hitter Luke Scott on a short fly to center and got Corey Patterson to foul out.
The Orioles managed only six hits, went 1-for-9 with runners in scoring position and stranded nine.
For a while, though, it was a tight game.
The Red Sox had runners at second and third with two outs in the first inning before Victor Martinez struck out, the first of 15 straight batters retired by Guthrie.
Baltimore appeared poised to end the scoreless duel in the fifth inning, using two singles and a bunt to put runners at second and third with one out. But Cesar Izturis hit a popup and Patterson grounded out.
In the sixth, Scutaro hit a liner to left that sailed inches outside the foul pole. The hit was ruled foul, and after umpires reviewed a replay, the call stood.
Scutaro struck out, but Dustin Pedroia singled to give Boston its first runner since the first inning. Pedroia then stole second before David Ortiz grounded out.
Boston recalled Reddick from Triple-A Pawtucket because Jeremy Hermida (arm, chest) was uncertain if he could play. RHP Scott Atchison was optioned to Pawtucket. … Baltimore has been held to one run or been shut out in seven of its last 10 games. … The season series is tied 4-4. … Baltimore's Matt Wieters broke an 0-for-20 slump with a ninth-inning double.