The Battle of Ontario turned out to be a one-sided affair after Fisher beat Leafs goaltender Andrew Raycroft twice in the first period and McAmmond added to the misery during a Toronto power play early in the second.
The Senators (39-23-6) had lost three straight games after blowing third-period leads, but the sold-out crowd of 20,018 at Scotiabank Place watched them take the lead early and run away with the game.
Ottawa improved to 5-1-1 against the Leafs (32-27-9) for the season and has won 12 of the last 15 regular-season meetings between the teams, outscoring Toronto 67-35 in the process.
Tom Preissing also scored on the power play, Daniel Alfredsson had three assists and Ray Emery stopped 28 shots to earn the victory in goal in the first game of a home-and-home series.
Jason Spezza returned after sitting out Ottawa’s shootout loss to Pittsburgh on Tuesday with a back injury and contributed two assists.
Dany Heatley also had an assist to extend his point-scoring streak to 13 games, during which he has 10 goals and 10 assists.
Alex Steen had the lone goal for the Leafs, who lost for the second time in three games and sixth time in the past nine contests.
Raycroft finished with 35 saves.
Toronto also lost its hold on the eighth and final playoff spot in the Eastern Conference standings. Although the Leafs are level with the New York Rangers, who won Wednesday, and Carolina, which was idle, on 73 points, New York has a game in hand.
The Senators went 3-for-6 on the power play; Toronto was 0-for-8.
The teams meet again Saturday at the Air Canada Centre.
After allowing just 24 shots in total in shutting out the Washington Capitals 3-0 on Tuesday, the Leafs were outshot 23-7 in the opening 20 minutes.
After the Leafs were called for too many men on the ice, Fisher took a pass from Peter Schaefer at the side of the net and beat Raycroft to open the scoring at the 5:13 mark.
Then, with Mats Sundin in the box for cross-checking, Fisher’s centring pass went off the skate of Leafs defenceman Carlo Colaiacovo and past Raycroft to make it 2-0.
At the other end, Bates Battaglia had Emery beat but rang a shot off the post and was later stopped from close range by the Senators goaltender.
The Senators’ 23 shots in the period were a season high.
Toronto had a four-minute power play that carried over to the second period thanks to a high-sticking penalty to Spezza and failed to take advantage.
With the Leafs back on the power play, they gave up a short-handed goal to McAmmond after some strong work by Alfredsson.
Steen cut the lead to 3-1 midway through the period, but Preissing scored on the power play after taking a cross-ice pass from Spezza before the second was over.
Spezza now has at least a point in the past 12 games he’s played.
McAmmond capped off the scoring with his second of the night early in the third.
Notes: Heatley’s assist was his 200th NHL helper. . . . Toronto forward Kyle Wellwood (hernia surgery) skated Thursday and could return for Saturday’s game. . . . In addition to defenceman Tomas Kaberle (concussion), the Leafs also scratched Wade Belak and forward Boyd Devereaux. . . . Defenceman Lawrence Nycholat, acquired from Washington on Feb. 26, has yet to dress for the Senators, who also scratched forwards Brian McGrattan and Patrick Eaves.