Reimer was replaced by Bernier after Ryan's shot from the right wing, which might have been deflected by a Maple Leafs defender, hit his right arm and fell into the net at 7:38.
"The third goal is a tough goal on [Reimer], but the reality is we left him hung out to dry," Maple Leafs coach Mike Babcock said. "[Bernier] came in and we did the same thing for [Bernier]. The lack of preparation as a team, which includes the coaching staff, not good enough. It's disappointing. We're in a building here, there was a ton of Toronto fans that paid to watch us play and they didn't get to see us play."
The Senators killed off three Toronto power plays in the first period.
The third penalty came when Stone was called for tripping Toronto forward Joffrey Lupul, whose skate came up and caught Stone in the face.
Stone went to the Senators dressing room, but returned shortly afterwards.
Zibanejad was penalized for an illegal check to the head on Toronto forward Tyler Bozak, who left the game and did not return.
Lazar scored the only goal in the second period. Shortly after Bernier made a nice glove save against him, Lazar was handed a rebound in the slot off a shot by Karlsson.
Lazar scored at 7:08. It was his first multi-goal game of his career.
Anderson made a few good saves in the second period, including a glove stop on Phaneuf during a 4-on-3 Maple Leafs power play.
Stone and Lazar scored early in the third period before Parenteau scored the Maple Leafs first goal at 3:25 when he put in a backhand into the open side to Anderson's left off a pass by Daniel Winnik.
"Losses like this hurt and I think you have to let them hurt for a little bit," Maple Leafs defenseman Morgan Rielly said. "Eventually you have to move on from it and start worrying about what's next."