Neuvirth was out for a month because of a lower-body injury, and after being activated from injured reserve Dec. 26, he played one period in the previous four games, replacing Brian Elliott for the third against the Penguins.
It was his first victory since a 33-save shutout against the Blues on Nov. 2 (five games).
"It's a huge win for me," he said. "I haven't been feeling good about myself lately. It's frustrating when you get injured and you can't help the teammates. I feel good about myself right now."
Neuvirth was strong in the first period when the Flyers were called for two penalties in the opening 3:42 and were outshot 12-5.
"It's always good when you face early shots and get to it right away," Neuvirth said. "I had a good warmup. I was feeling good all morning. Penalty kill stepped up big for me there."
Among his biggest saves was a lunging glove stop on Sam Reinhart at 5:04 of the first period.
"That was a huge save there," Flyers forward Jakub Voracek said. "We took two penalties early in the game and [Neuvirth] was huge. … He made a couple huge saves in the game and we just focused on ourselves on the ice and not let them have many scoring chances. When we did [Neuvirth] was big."
O'Reilly scored on the power play at 1:50 of the second period to give the Sabres a 1-0 lead.
Gostisbehere tied the game 1-1 less than two minutes later after he broke up a play in the neutral zone, then joined the attack, took a return pass off the rush from Scott Laughton, and beat Lehner at 3:42.