Patrice Bergeron recorded two goals and an assist as visiting Boston opened up a five-point advantage in the Northeast Division over Ottawa.
David Krejci netted the game-winner on a power play in the third period and Brad Marchand recorded his career-high 22nd goal for Boston, which completed its longest road trip of the season with a 3-2-1 mark.
The Bruins gave up the first tally but wasted little time battling back, with Bergeron knotting it at 1-1 early in the first period. Boston appeared to be running away late into the third period as Krejci's 13th goal pushed it to 4-1.
The Senators made things interesting late with two similar goals by captain Daniel Alfredsson. A one-timer from the left boards cut it to 4-2 with 3:45 left and the second tally came from almost the exact same spot 1:37 later.
Boston goaltender Tim Thomas slammed his stick against the post in frustration.
Bergeron put it out of reach with an empty-net goal to close it out.
The highlight for the Bruins came in the second period, when rookie Carter Camper banged in a rebound for his first NHL goal, making it 3-1.
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GAME NOTEBOOK: The Bruins host the Senators on Tuesday ... Ottawa C Jason Spezza recorded three points to reach 601 for his career. Spezza has 19 points in his last eight games. ... Alex Auld started in goal for the Senators with Craig Anderson (hand) out.