Three weeks into the 2015 season, the Orioles find themselves in last place after absorbing a fifth consecutive defeat.
The five-game skid is the Orioles' longest since September 2013.
"We have to grind through it," manager Buck Showalter said. "Nobody's going to feel sorry for us. This is not the type of club that's going to wallow around in self-pity."
After Tommy Hunter retired the first two Boston batters in the eighth, Brian Matusz (0-2) walked Pablo Sandoval. Pinch-hitter Allen Craig followed with a sharp bouncer off O'Day that skipped past Machado, who was charged with an error.
"Manny's as good a third baseman as you can find," Showalter said. "He's bailed us out a lot of times."
Holt then brought home three unearned runs with his fifth career homer.
"It was fun," Holt said. "We needed to get some runs there."
Miguel Gonzalez allowed four runs and eight hits in six innings for Baltimore. It was only the fifth time in his last 30 starts that the right-hander yielded as many as four earned runs.
Boston starter Rick Porcello gave up four runs and six hits in six-plus innings. In his previous outing, also against Baltimore, the right-hander allowed eight runs and a career-high 12 hits.
Porcello struck out the first five batters he faced and didn't give up a hit until Machado singled with one out in the fourth. Paredes followed with a shot to right for a 2-0 lead.
The advantage didn't last long.
Gonzalez retired the first two batters in the fifth before Mookie Betts walked and Dustin Pedroia singled to set the stage for Boston's first back-to-back homers of the season. David Ortiz hit a three-run drive to right that barely cleared the outstretched glove of a leaping Delmon Young, and Hanley Ramirez crushed a no-doubt shot to left.
Baltimore got a run back in the bottom half when Rey Navarro doubled and scored on a single by Cabrera. Navarro was playing in his first major league game after a long run in the minors that began in 2007.
Red Sox: Boston was 12 for 12 on stolen base attempts before Pedroia was caught in the seventh inning, confirmed by replay. ... The Red Sox reached double digits in hits for the first time in nine games. ... Boston has won all six of its series openers. ... Ortiz has six homers in his last 12 games in Baltimore.
Orioles: Baltimore has 24 homers in 17 games. ... Davis has nearly twice as many strikeouts (27) as hits (14). ... In six games since being activated from the disabled list, Paredes is 8 for 25 (.320) with two homers and six runs scored.
Red Sox: RF Shane Victorino missed a second straight game with a sore right hamstring. The injury occurred Wednesday night against Tampa Bay.
Orioles: Baltimore placed INF Ryan Flaherty on the 15-day disabled list with a right groin strain and recalled Navarro from Triple-A Norfolk.
Red Sox: Justin Masterson (2-0, 5.74 ERA) seeks his second win over the Orioles in a five-day span Saturday night.
Orioles: Wei-Yin Chen (0-1, 3.07 ERA) issued five walks and gave up five unearned runs in a loss to Boston on Monday. ... Showalter will miss Saturday's game to attend the funeral of his father-in-law.