Tyler Ennis had a hat-trick while Drake Batherson and Alex Formenton also scored for the Senators (13-20-3) as Matt Murray made 32 saves. Aaron Dell stopped 42 shots in the Buffalo (13-22-7) net.
"We're playing some good hockey right now and we're growing as a team and personally, it feels good to put the puck in the net," Ennis said.
However, the game was marred by a controversial hit by Dell on Batherson in the first period that saw the Senators All-Star leave the game and not return.
"It's unfortunate for him," Sens head coach D.J. Smith said. "The kid has a chance to go to his first All-Star game. It's a bad play by the goalie … it's ridiculous."
It was an eventful first that initially saw a Buffalo goal waved off as the whistle was blown moments before Jeff Skinner scored as Dylan Gambrell was injured down the other end of the ice after he was hit high by Rasmus Dahlin.
After Casey Mittelstadt and Tim Stützle traded posts, the Senators opened the scoring at 15:53 through Ennis' first goal since opening night as on an odd-man rush, he finished Adam Gaudette's centering feed after he had danced around Robert Hagg.
The Senators' lead was doubled at 17:11 as Batherson was credited with a power play goal on a strange one as Stützle's shot hit the back of Batherson's skate, hit the crossbar and bounced into Mattias Samuelsson who not once, but twice, swatted the puck with his stick, but saw his second effort fly into the net as the Sens' All-Star scored his 13th of the season.
Ennis' second of the night came at 18:48 as he buried from in-close off of Chris Tierney's pass before disaster struck for the Sens as Batherson was injured after he was hit by Dell while he was forechecking.
"It's tough to see him go down," Ennis said. "He's having such a great season. He's a great teammate and it's disappointing as he was going to his first All-Star game … it's unfortunate and unnecessary."
Ottawa scored the lone goal of the fourth and it came on Formenton's eighth as on a 2-on-1, he fed Stützle who would return the favour at 11:15 as Formenton guided the puck into the empty net.
Ennis rang the crossbar with 3:52 left but he wouldn't be denied his second career hat-trick as he fired a low wrister past Dell's blocker with 29.3 seconds left in the third.
"It was nice of D.J. to keep putting me out and try to get [the hat-trick]," Ennis said. "It felt pretty good to see that third one go in."
Murray recorded his third shutout as a Senator and the 14th of his NHL career.
"He made some huge saves in the third," Smith said. "We gave up some chances that we shouldn't have given up in the third but he made the saves. He saw everything. He looks as good as he's looked since he's been here."
In addition to Batherson, Gambrell also didnt return to the game after being injured in the first.
"Gambrell will likely be out a week, a little bit less, maybe," Smith said. "Drake looks like it will be a lot longer."
Ottawa is back in action Thursday when they host Carolina at 7 p.m.
