Jeremy Guthrie (9-17) allowed four runs on 10 hits over six-plus innings to earn the win. He struck out three and walked one.
Jim Johnson tossed a 1-2-3 ninth to record his seventh save of the season.
Matt Angle hit a two-run double for the Orioles, winners of five of their last six.
Kyle Weiland (0-3), making his fifth career start, allowed six runs -- five earned -- over 4 2/3 innings to suffer the loss.
Adrian Gonzalez went 2-for-4 with a double and two RBI for the Red Sox, who saw their lead in the AL wild card race cut to 1 1/2 games over the idle Rays.
They are just 4-14 in the month of September and dropped three of four to Tampa Bay over the weekend. Additionally, they are 5 1/2 games behind the AL East-leading Yankees, who beat the Twins, 6-4, Monday.
"We're not quitting," said Red Sox second baseman Dustin Pedroia. "We've got the lead. We've got to go out there and play better. I'm not hanging my head."
Hardy's leadoff homer gave the Orioles a 6-2 lead in the top of the fifth, but the Red Sox pieced together a two-out surge in the home half to remain close.
After groundouts by Darnell McDonald and Jacoby Ellsbury, Marco Scutaro drew a walk to keep the inning alive. Gonzalez followed with an RBI double and scored on Pedroia's subsequent triple off the wall in center to make it a 6-4 game.
David Ortiz then ripped a line drive off the short wall in right. Though replays proved him wrong, first base umpire Mike Estabrook called the ball foul and Ortiz eventually flew out to end the inning
In the seventh, Guthrie was pulled after allowing a leadoff single to McDonald. Troy Patton entered and induced Ellsbury into a 4-6-3 double play but Scutaro followed with a double down the left field line and Gonzalez's single pulled the Red Sox within a run. Willie Eyre lined out Pedroia to prevent further damage.
"We battled and battled and battled," said Red Sox manager Terry Francona. "I'm glad we're playing again."
In the first, Pedroia grounded into a 6-4-3 double play, stranding runners at first and second.
An inning later, Josh Reddick doubled with one down when Reimold lost a fly ball in the sun in left field, but Guthrie retired the next two batters.
In the top of the third, Reimold tallied a measure of revenge, reaching first with a fly ball to left, which McDonald lost in the sun.
Things didn't get better for McDonald, who was a late addition to the lineup due to Carl Crawford's stiff neck. Josh Bell followed with a fly ball into left-center, which bounced off the heel of McDonald's glove, allowing runners to reach the corners.
Angle then belted a ball off the left field wall, just out of the reach of the leaping McDonald, giving the Orioles a 2-0 lead.
The left fielder atoned for his struggles with a leadoff shot in the home half, but Andino's two-run blast in the fourth was followed immediately by Reimold's homer over the Green Monster for a 5-1 Orioles lead.
Jarrod Saltalamacchia tripled home Ortiz in the bottom half to make it a 5-2 game.
Hardy hit his 28th home run of the season...The Red Sox stranded five and were 2-for-8 with runners in scoring position...Baltimore went 1-for-8 with runners in scoring position and left seven men on base.