Chad Johnson had 26 saves for the Sabres, who won for third time in four games and spoiled the 400th head-coaching game for Tampa Bay's Jon Cooper.
Nicholas Baptiste and Scott Wilson also scored for Buffalo, which won for just the eighth time at home (8-16-4) this season.
Ryan Callahan, Yanni Gourde and Vladislav Namestnikov scored goals and Louis Domingue had 28 saves the Eastern Conference-leading Lightning, who saw their lead in the Atlantic Division dwindle to just one point with Boston a 5-2 winner over Calgary.
Baptiste, called up from Rochester of the AHL to replace leading scorer Jack Eichel (sprained right ankle), gave the Sabres a 1-0 lead off a pass from the left corner from Zemgus Girgensons, which Baptiste fired through the pads of Domingue.
Gourde, stationed in front of the net, tied it at 13:23 with his 22nd goal of the season and eighth in 11 games on the a power play, deflecting Nikita Kucherov's pass from the left circle through Johnson's pads.
Reinhart put Buffalo back in front, 2-1, at 1:16 of the second period when he tapped in a rebound of an O'Reilly shot on the power play into a wide-open left side of the net. The Lightning came back to tie it when Callahan pressured Johnson, who was trying to clear the puck, into an errant pass in front of his own net, where an uncovered Namestnikov tapped it in.
Wilson gave the Sabres a 3-2 lead when Casey Nelson's shot from the point redirected off his shin past Domingue. O'Reilly made it 4-2 with a rebound goal of a Kyle Okposo shot at 3:41 of the third period. Callahan pulled the Lightning to within 4-3 at 11:36 with his third goal of the season, but Reinhart sealed the win for the Sabres with an empty-net goal with 7.1 seconds left.
--Field Level Media
Tampa Bay | Buffalo | |
Ryan Callahan 1 | Points | Ryan O'Reilly 3 |
Ryan Callahan 1 | Goals | Sam Reinhart 2 |
Victor Hedman 1 | Assists | Ryan O'Reilly 2 |
Yanni Gourde 1 | Power Play Goals | Sam Reinhart 1 |
N/A | Short Handed Goals | N/A |
Louis Domingue .875 | Save Percentage | Chad Johnson .897 |
Louis Domingue 28 | Saves | Chad Johnson 26 |
Team | Shots | Goals | Power Play | Penalty Kill | Penalty Mins | Face Offs Won |
Tampa Bay | 29 | 3 | 1-5 | 1-3 | 6 | 36 |
Buffalo | 33 | 5 | 2-3 | 4-5 | 10 | 37 |