"I probably never had that big a goal in my life," the 19-year-old defenseman said. "It's a great feeling and I'm going to try to do it again."
Zadorov took a crossing pass from Tyler Ennis and scored 29 seconds into overtime to cap the comeback victory, Buffalo's third in a row and ninth in the past 12 games.
Brian Gionta scored the tying goal with 14:33 left in regulation for the Sabres, who have overcome third period deficits in four of their last five wins.
Marcus Foligno and Cody Hodgson also had goals for Buffalo and Jhonas Enroth made 25 saves.
"The team feels good about themselves," coach Ted Nolan said. "They're playing hard for one another and when you do that good things happen. So right now, knock on wood, things are going good for us."
Jussi Jokinen, Sean Bergenheim and Jimmy Hayes scored goals for Florida (12-8-8), which had won its last five meetings with Buffalo.
Backup goaltender Al Montoya stopped 28 shots for the Panthers, who picked up three points on a three-game road trip after losing Monday in St. Louis and winning in a shootout Friday in Detroit.
"Overall we got three points in three tough buildings," Panthers coach Gerard Gallant said. "Not happy, but, I guess, satisfied going home."
With the Panthers playing on short rest, the Sabres were the aggressors early, firing off the first four shots of the game and taking the lead on Hodgson's goal 2:06 into the first period.
Zadorov had the secondary assist on Hodgson's goal, giving him his first career multi-point game. Pat Kaleta set up the goal with a backhand pass from the boards. It was Kaleta's first point of the season and his first assist since March 7, 2012.
Foligno scored to make it 2-0 with 6:55 left in the first period. It was the sixth time in seven games the Panthers have fallen behind in the first period.
"We have to be better in the first period," Florida defenseman Brian Campbell said.
Campbell brushed off the suggestion that playing on the second night of a back-to-back contributed to the Panthers' poor start.
"I don't think good teams use that excuse," he said.
Florida was better in the second period, scoring on its first two shots to tie the game less than five minutes in.
Bergenheim knocked the puck in off Zadorov's skate 1:08 into the period, then sent a pass across the crease to set up Hayes tying goal at the 4:51 mark.
Zadorov was on the ice for both of the Panthers' second-period goals.
"That was just a bad couple of shifts, bad couple bounces, bad couple goals," Zadorov said. "I just forgot about that, stepped on the ice and did my job."
Jokinen gave Florida its first lead 57 seconds into the third period, scoring on a slap shot from the right circle off a crossing pass from Dave Bolland.
Gionta took a long pass from Tyler Myers and scored on a wrist shot from the top of the right circle to tie the game 3-3 with 14:33 left in the third period.
NOTES: The Sabres were down to four healthy defensemen by the end of regulation. Andrej Meszaros left the game in the second period after he was hit in the face by a deflected shot. Josh Gorges, Buffalo's alternate captain, was injured while blocking a shot in the third period. Nolan said both players will miss Monday's game against Ottawa. . Sabres D Mike Weber underwent surgery on his left knee Friday and will miss about two weeks, coach Ted Nolan said. . Florida has gone to overtime in 11 of its 28 games, tying Anaheim for the most in the league.