Peter Holland scored the go-ahead goal 5:28 into the third period against injured goalie Al Montoya, and the Maple Leafs held on for a 3-2 win that snapped Toronto's franchise-worst 16-game, road-losing streak.
Montoya was injured earlier after relieving starting goalie Roberto Luongo, who got hurt in the first period and didn't come out for the second.
It was Toronto's first road win since a victory at Boston on Dec. 31 (0-14-2).
"Nice to get a win here on the road and get a good feeling in the room again," Holland said.
The Panthers changed goalies twice, and even had goalie coach Robb Tallas get dressed on an emergency basis, but the 41-year-old Tallas never entered the game. He hasn't played in an NHL game since 2001.
Montoya was injured early in the third period, but managed to stay in the game despite being hobbled with a groin injury. He eventually was replaced by Luongo, who got back into uniform after changing into street clothes.
Luongo was injured with 4:03 left in the first period when he was hit with the puck on the side of the head on a wrist shot by Leo Komarov. Luongo was treated by trainers for several minutes, but remained in for the rest of the period.
Luongo came back on with 9:08 left in the game. Montoya finished with 13 saves. Luongo stopped 19 shots.
Panthers general manager Dale Tallon said his team was in contact with the NHL and trying to get Tallas cleared to play. While that process was ongoing, the Panthers decided to have Montoya return to the game.
Tallas was ultimately cleared, but Luongo wound up being the one who replaced Montoya. Luongo had a CT scan performed during the game, Tallon said.
"It's rare. Doesn't happen very often," Tallon said. "You're in constant communication with the league to do the right thing, and you have to have him be legal and it has to be cleared by central registry.
"It's hard to do that at 11 o'clock or 10:30 at night. ... If we couldn't get him cleared, it would have had to be a player."
Tallon said the Panthers also entertained the notion of putting Derek MacKenzie in the game.
"Louie decided he would give it a shot," Tallon said.
The Panthers gave no specifics on the severity of either injury, though Gallant said Montoya is "hurt pretty good." Tallon said it was likely that the team will summon a goalie for practice on Wednesday.
Nazem Kadri and Tyler Bozak also scored for the Maple Leafs, and Jonathan Bernier made 40 saves.
Aaron Ekblad and Brandon Pirri scored for Florida, which lost for the first time since Jaromir Jagr joined the team on Thursday. Jagr had four shots in 18:30 of ice time.
"We're playing a pretty good game, and all of a sudden, boom, boom, you lose two goalies real quick," Panthers coach Gerard Gallant said. "Fortunately for us, both of them were able to return and play some of the game, and Robbie (Tallas) didn't have to go in there. But there was a lot of confusion going on."
Holland put the Maple Leafs ahead for good when he corralled a rebound in front of the net and poked the puck past Montoya. Holland said he could tell Montoya was hurting.
"I think if he was feeling 100 per cent he would have gotten across the net there," Holland said. "That's not typical Montoya. He's usually pretty quick along the bottom there. They don't ask how and I won't ask how, either."
The Maple Leafs had tied it 2-2 on Kadri's goal 22 seconds into the third. The puck rebounded sharply off the boards, and Kadri got behind Montoya to sweep in the puck.
Montoya collided with Kadri and was slow getting up.
"He's hurt pretty good, lower body," Gallant said. "But he battled and he found a way to compete there for us. He did everything he could."
Ekblad put the Panthers ahead 2-1 with a power-play goal. Ekblad took a pass in the high slot and one-timed a shot past Bernier on the glove side at 13:12 of the second.
The Maple Leafs have allowed a power-play goal in seven of their past eight games.
Bozak tied it 1-1 with a power-play goal in the second period. Phil Kessel took a shot that was blocked, and Dion Phaneuf and Bozak scrambled for the loose puck in front.
Bozak poked it in at 4:40 for Toronto's first goal since Feb. 26 against Philadelphia when Phaneuf scored at 1:22 of the third period. The Maple Leafs went scoreless for 163 minutes, 18 seconds.
The Panthers took a 1-0 lead on Pirri's goal. Jimmy Hayes passed the puck to Pirri in the slot for a wrist shot that went between Bernier's pads with 17.2 seconds left in the first.
It was Pirri's third goal in three games since he missed nine due to an upper-body injury. The Panthers are two points behind Boston for the final playoff spot in the Eastern Conference.
"It was unfortunate we let this one slip away. These are two big points we needed," Pirri said.
NOTES: Forward Joakim Lindstrom, acquired Monday from St. Louis, made his Maple Leafs debut. ... Ekblad set the Panthers record for goals by a rookie defenceman with 11. He broke Ed Jovanovski's mark that was established in the 1995-96 season.