A giveaway in his own slot by Marcus Foligno gave Tomas Fleischmann a 1-on-1 with Enroth midway through the first, but the Sabres' goalie made a right pad save to keep the game scoreless.
Luongo was called upon to make a pair of close-range shots on Matt Moulson early in the second.
Foligno had a wraparound attempt in the third period's first minute, but Luongo slid over to stop the puck with his left pad.
"You got that guy back there and your team is so much more confident," said Panthers defenseman Erik Gudbranson. "He made really good saves all night. It's amazing how he tracks the puck within those scrambles and is able to come up with pretty key saves."
The Sabres wasted a prime opportunity when they had a 5-on-3 power play for 49 seconds in the third period. Luongo made a pair of saves before Erik Gudbranson's penalty expired, then three more by the time Chris Stewart ended the power play by taking down Upshall in the slot.
"(Luongo) made four, five saves in the third period, like real key saves for us," Gallant said. "Especially that 3-on-5 when the guys did a great job killing that so those were definitely key points in the hockey game and I thought our group stood up real good."
Buffalo again had a slow start, with just three first-period shots on goal, and failed to build on Tuesday's win in Carolina.
"We're definitely not happy," Sabres coach Ted Nolan said. "No one's going to help us get out of this thing except for ourselves. We got a good group of guys. We just got to learn we have to compete and we have to work. We're not a fancy team."
With Florida's Aaron Ekblad and Buffalo's Sam Reinhart, the game also marked the earliest season match-up between the NHL's No. 1 and No. 2 draft picks since 1997, when Boston's Joe Thornton and San Jose's Patrick Marleau faced off.
Luongo, drafted No. 4 overall that year, began the day with a 1.93 goals against average, .938 save percentage in 19 career games against the Sabres.