Twenty-five seconds later, Devon Toews put Colorado back in front 3-2 at 8:33 on a rebound.
"I like our response after they made it 2-2 probably the best," Avalanche coach Jared Bednar said. "I thought we were playing a good hockey game up 2-0. Once they got those two and the building started going, I was getting a little nervous about what our response would be. And then right away we answer and score to get the lead again. So I like to stick-to-itiveness of our team tonight."
MacKinnon made it 4-2 at 14:01 with a power-play goal from the slot after the puck bounced to him.
Aleksander Barkov cut it to 4-3 at 11:03 of the third period when he tapped in Reinhart's centering pass. Barkov missed Florida's previous game, a 4-1 win against the San Jose Sharks on Thursday, with an upper-body injury.
"We did not get the start we wanted," said Barkov, the Panthers captain. "They dominated us in the first period. I don't know what happened there, but we came back and played a solid game at the end. We just did not get the goal or get the win at the end."
MacKinnon scored into an empty net at 19:01 for the 5-3 final.
"We felt calm all night," MacKinnon said. "I think even at the end there. I thought we handled that PK, the 6-on-5 really well. Just great to see."
NOTES: Avalanche All-Star defenseman Cale Makar missed a second game because of an upper-body injury he sustained when he was hit in the head by Pittsburgh Penguins forward Jeff Carter on Tuesday. He is day to day. … Colorado defenseman Erik Johnson left the game in the first period with an upper-body injury. There was no update. … MacKinnon scored the 47th game-winning goal of his NHL career, tying Michel Goulet for third in franchise history behind Joe Sakic (86) and Milan Hejduk (59). ... The Avalanche used 11 forwards and seven defensemen. … Tkachuk has 17 points (five goals, 12 assists) in his past nine games.