Dany Heatley had a goal and assist for Ottawa, which rebounded from a 6-0 loss at Nashville on Thursday. Ray Emery made 35 saves for the Senators, who have handed the Sabres three of their six regulation losses this season.
Jochen Hecht scored for Buffalo, which had its winning streak snapped at three. Ryan Miller, who lost for the second time in his last eight decisions, made 26 saves.
Spezza had an opportunity for a hat trick, but missed a penalty shot with 12:50 remaining.
Heatley opened the scoring at the 5:42 mark of the first period, swiping in a puck that was already going into the net. Andrej Meszaros took a shot from the point and it was tipped by Buffalo's Thomas Vanek before going through Miller's legs. The puck was creeping toward the goal line when Heatley tapped it for his team-high 19th goal of the season.
Spezza made it 2-0 with a power-play goal with 2:31 remaining in the opening period. He was stationed on the left side of the slot and completed a tic-tac-toe play that Heatley began from behind the Buffalo net.
In the second period, Hecht reduced the lead to 2-1 on a power-play goal with just under six minutes remaining. Brian Campbell fired a shot from just inside the blue-line, and Hecht tipped it while in the slot.
Spezza netted his second of the night, raising his season total to 19, when he lifted a shot over a prone Miller after Andrew Vermette fed a drop pass from the slot.
The Sabres had one power-play chance while trailing 3-1, but mustered only one shot on Emery.
Notes: Ottawa captain Daniel Alfredsson returned to the lineup after missing five games with a hip injury. F Peter Schaefer also came back from an eye infection which sidelined him for one game. D Wade Redden was out for an eighth game with a chest injury. ... Buffalo was 1-of-6 on the power play, but have converted only five of their last 56 opportunities. Ottawa scored twice in four chances. ... Spezza has a point in 11 of 12 games. ... Heatley broke a five-game streak without a goal, matching his season long streak. He has not gone six games without a goal since 2001-02, his rookie season.