Ottawa scored three goals in the first period and held on for a 4-3 victory on Wednesday night that sent the Maple Leafs into the NHL All-Star break on a six-game losing streak.
The Senators rebounded after losing in overtime at the New York Rangers on Tuesday night.
"I scratch my head when I talk about that first period again," Maple Leafs interim coach Peter Horachek said. "That was totally done by ourselves, to ourselves, to a team that played (Tuesday) night.
"We wanted to play more like we played in the second and third period and come out with some energy and put more pucks to the net and create more chances, but it's a strange situation so we've got to correct that for sure."
Toronto, 1-7 under Horachek, has just three wins in its last 17 games.
Erik Karlsson scored two goals, Mike Hoffman and Mika Zibanejad had one each, and Craig Anderson stopped 37 shots for the Senators (19-18-9).
David Clarkson, Nazem Kadri and James van Riemsdyk had goals for the Maple Leafs (22-23-3).
"We just have to keep trying to move forward," Kadri said. "That's really all we can do is try and stay positive. We just have to play with that desperation through 60 minutes instead of 40 or 45."
James Reimer made 22 saves and lost for just the second time at Ottawa (8-2).
"We didn't have a good start," Reimer said. "Obviously, you can't get down 3-0 and then expect to win in this league. I thought we did a great job of battling back and working hard in the last 40 minutes, but just ended up falling a bit short."
Toronto made things interesting when Kadri's power-play goal at 2:36 of the third period cut the Maple Leafs' deficit to 3-2. Kadri took a pass from Morgan Rielly and beat a screened Anderson.
The Maple Leafs pressed for the tying goal, but they were unable to create any real solid scoring chances.
With 4:40 remaining, Karlsson scored his second of the night to make it 4-2. Milan Michalek grabbed the puck behind the net and found Karlsson just inside the blue line for a shot that beat Reimer to the glove side.
Van Riemsdyk scored with 1:23 left, but Toronto was unable to complete the comeback.
"It was a big win for us," Anderson said. "We make sure the fans get everything they pay for when we make it close at the end.
"I had confidence in the guys that we were going to get the job done. We made sure that we got the puck out of our zone to end the game, and that's huge for us to get some confidence heading into the break. We can come back hopefully feeling good about ourselves and we can continue to play well."
Trailing 3-0 after 20 minutes, the Maple Leafs had a better second period but were only able to beat Anderson once. Clarkson, with his second goal in 20 games, got the Leafs on the board 13:55 into the middle period.
The Senators nearly regained the three-goal lead late in the frame, but Reimer stopped a 2-on-1 to keep Toronto within reach.
The Maple Leafs had an opportunity to score in the opening minutes of the game as Phil Kessel had a breakaway, but his shot went wide of the net. Less than a minute later, Mark Stone — who extended his point streak to seven games with an assist — fed Hoffman at center ice for a shot that beat Reimer under the crossbar.
Midway through the period, Karlsson capped off a great give-and-go with Hoffman for his 10th goal of the season.
The Senators capped the period scoring on a delayed penalty call when Bobby Ryan found Zibanejad alone.
"We came out strong and definitely got the advantage right off the hop," Hoffman said. "We knew they were going to come back and make a strong push. They got a few, we got a few, and our goalie played well."
NOTES: D Chris Phillips, C Colin Greening and C David Legwand were healthy scratches. C Zack Smith (wrist) and D Mark Borowiecki (leg) remained sidelined for the Senators. ... Toronto D Stephane Robidas and D Korbinian Holzer were healthy scratches. Maple Leafs center Leo Komarov was out due to a lower-body injury.