Two days earlier, Florida used a four-goal third period to defeat Carolina by the same 4-2 score.
"We played solid in the second period, played smart, and didn't make many mistakes," said captain Olli Jokinen, who closed out the scoring blitz with his sixth goal in the last five games and eighth overall. "We got all four lines going and waited for them to make mistakes."
Radek Dvorak also scored for the Panthers, who won for only the second time in seven road games despite not getting a power-play opportunity.
"We won the game in Carolina and felt good, so we knew we could play a good game coming in here," Zednik said. "It's a huge win for us."
Vokoun, making his sixth straight start, made several solid stops in the first period before the Panthers erupted for the three second-period goals on 17 shots.
"When you play on the road you have to play your system real well, and that's what we did," said Vokoun, who has allowed four goals in his last two games after giving up 15 in his previous four outings. "There's no secret how you have to play when you want to win."
Jochen Hecht and Thomas Vanek scored for slumping Buffalo, which has lost five of its last seven, including an overtime loss to Boston on Thursday. Last season's President's Trophy-winner dropped below .500 for the third time already this season.
"It's pretty frustrating right now," defenseman Brian Campbell said. "I thought we played well in the first period, but that's just one period."
Sabres goalie Jocelyn Thibault was making just his second start of the season and first in nearly three weeks. He made 20 saves.
"We hung him out to dry," Sabres coach Lindy Ruff said about his No. 2 netminder. "We were flat-out awful at times. They got us on a run a little bit and we didn't do a lot about it."
Dvorak opened the scoring with his first of the year at 5:32 of the first period, backhanding a rebound past Thibault.
Hecht tied it with his fourth goal 9 minutes into the second period when he also backhanded a rebound in.
The Panthers then broke the game open by scoring three straight goals in a 5:02 span, starting with Zednik's tally with 6:25 left in the middle frame. Standing a couple of feet from the top of the crease, Zednik tapped in Jozef Stumpel's cross-ice pass for a 2-1 Florida lead.
Zednik made it 3-1 with his fifth of the season 3 minutes later, putting home his own rebound after Sabres defenseman Andrej Sekera blocked his initial shot.
Jokinen increased the lead to 4-1 after converting a nifty tic-tac-toe passing play that also involved Nathan Horton and Ville Peltonen.
"I thought we had the game pretty under control," Florida coach Jacques Martin said. "We made good decisions, and in the early part of the season that's where we were having trouble."
Vanek cut the deficit to 4-2 with a power-play goal with 3:23 left in regulation.
Ruff coached his 750th NHL game, the 31st coach in history to reach that plateau. ... Martin coached his 1,029th NHL game, and moved into sole possession of eighth place on the all-time list. ... Sabres D Nolan Pratt made his debut, but sustained a groin injury that limited him to three shifts in the third period. Pratt was signed to a one-year deal on Thursday. ... Buffalo D Jaroslav Spacek missed his sixth game in the last seven because of a shoulder injury. ... The Panthers won for the first time in their last four games in Buffalo.
Copyright by STATS LLC and The Associated Press
Arena: First Niagara Center Location: Buffalo, New York
Referees: Ian Walsh Linesmen: David Brisebois, Brad Kovachik