Though they hit several balls hard, and had some knocked down by a gusty wind, the Sox went 0-for-10 with runners in scoring position while leaving 12 men on base.
The only impactful hit the Sox had was from Grady Sizemore, who belted an equalizing solo shot in the fourth inning while playing his first game in the Majors since Sept. 22, 2011.
"We created a number of opportunities obviously," said Farrell. "I thought we squared up a number of balls that got knocked down by some gusty winds in the outfield. But we continue to create chances. I thought Jon Lester was in control of the ballgame here today. They made the most of the hits they put up."
Lester lost control of the game for one brief moment, and that was enough to cost him the game.
Nelson Cruz had the biggest hit of the day, a solo shot to left against Jon Lester on the first pitch of the bottom of the seventh to snap a 1-1 tie.
"He's a great pitcher," said Cruz, who was making his debut with the O's. "He's one of the elite pitchers in the league. It's baseball. Anything can happen."
It turns out it wasn't even a misfire.
"Fastball," said Lester. "I felt like he hit a pretty good pitch."
The Red Sox came tantalizingly close to offsetting the big blast by Cruz.
In the eighth, Mike Napoli led off with a walk and Xander Bogaerts came through with a two-out walk, setting the table for A.J. Pierzynski.
When lefty Brian Matusz came out of the bullpen for Baltimore, Farrell opted not to go to right-handed power threat Jonny Gomes.
"Well, A.J. is going to put the bat on the ball," said Farrell. "Left-handed, right-handed, A.J. is going to put up a good at-bat. Still, we had a number of opportunities. The two-out base hit was elusive."
It haunted the Sox yet again in the ninth. Facing closer Tommy Hunter, Will Middlebrooks represented the tying run when he was hit by a pitch to start the inning. Dustin Pedroia rifled a single up the middle, and David Ortiz was looming.
But Ortiz flew out to left, leaving the game in the hands of Jackie Bradley Jr., who was recalled from Triple-A Pawtucket earlier in the day and came on an inning earlier as a pinch-runner for Napoli.
Bradley fell behind 0-2 and wound up striking out looking on a 93-mph heater to end the game.
"I didn't think it was a strike," said Bradley. "Didn't think the first one was a strike either. That's just the way it goes."
The game-ending pitch did appear to cross the strike zone, according to television replays.
"I thought he fought back into the count well," said Farrell. "He gets down 0-2 and then he takes a couple of borderline fastballs. He laid off a good breaking ball that was on his back foot. You know what? He just misses a fastball in the middle of the plate [for a foul ball]. Strike three was a strike. It wasn't up, it was on the plate. He battled."
Making his fourth consecutive Opening Day start, Lester had a solid day, giving up six hits and two runs while walking one and striking out eight. He threw 104 pitches, 73 for strikes.
The Orioles broke out first, as Cruz opened a second-inning rally with a walk and Matt Wieters blooped in a single to put runners at the corners with nobody out. Delmon Young hit a slow roller to second, and Pedroia turned into an unusual 4-3-6 double play, with Cruz scoring to make it 1-0.
Sizemore had already celebrated his comeback by belting a single to right in his first at-bat.
In the fourth, Sizemore made an even bigger stamp on the game, clubbing a 3-1 pitch by Orioles ace Chris Tilman over the wall in right.
Nobody was more surprised than Sizemore that the ball left the yard, considering he broke his bat on the swing.
"It was exciting at the time," said Sizemore. "It's a nice feeling to get that first one. Just going through what I've gone through, it felt nice to get that moment."
The Red Sox hoped they would have other moments to celebrate, but they never came.
In the second inning, Bogaerts nearly drilled a three-run homer, but the drive was right into the teeth of the wind and Cruz hauled it in.
"It looked like a home run or a double off the wall, easy," said Mike Carp, who singled to open the inning. "It just carried. The way Nelson was going towards the ball, I wanted to make sure I could score, and he ended up coming up with the catch."