Robin Lehner made 32 saves for his first career 0 victory on Tuesday night.
Erik Karlsson scored the game's only goal on a slap shot in the first period as the Senators improved to 6-1 in their last seven outings.
Lehner, 20, made 17 saves in the third period to wrap up his first shutout in 11 NHL games. He also beat the Islanders 5-2 on Sunday in his second start of the season and first since October 30.
The youngster was called up after regular starter Craig Anderson lacerated the pinky finger on his right hand.
Tim Thomas was a hard-luck loser after allowing just one goal on 38 shots for Boston. The Bruins were shut out for the seventh time this season, and fifth time in February.
The Senators have 76 points, one fewer than Boston. They snapped an eight-game losing streak to the Bruins, including a four-game skid in the season series.
The teams will play just one more time, on April 5 in Ottawa.
The Bruins were coming off a win over the Senators in Ottawa on Saturday to end a 3-2-1 road trip. It's wasn't a true home-and-home series because the Senators hosted, and beat, the Islanders on Sunday.
Veteran forward Brian Rolston, acquired before Monday's trade deadline, played eight minutes for the Bruins and was whistled for a tripping penalty in the first period.
"I'm very happy to be here. I got a warm reception from the crowd, which was nice," said Rolston, who played for Boston from 2000-04.
It was Tyler Seguin's interference penalty that led to Karlsson's power-play goal with 5:16 remaining in the first period.
Daniel Alfredsson was screening Thomas in front when Karlsson drifted to his left at the point and rifled a slap shot that beat the Boston goaltender to make it 1-0.
Thomas kept the Bruins in it. Among his saves was a stop on Zack Smith's breakaway with just over four minutes remaining in the third period and the Senators looking to seal the win.
Anderson is sidelined indefinitely...The Bruins started a three-game homestand that also includes visits from the Devils and Islanders. Defenseman Mike Mottau also made his debut for Boston after he was acquired from the Islanders in the same deal that landed Rolston. Mottau played more than 10 minutes...The Senators got defenseman Matt Gilroy in a deal with Tampa Bay before the trade deadline and he played almost 15 minutes.