Winnipeg came into the game barely holding on to the eighth seed in the Eastern Conference, but now holds a three-point lead over Washington and is just two points back of Florida for the lead in the Southeast Division.
Corey Tropp scored the only goal of the game for the Sabres, who had a three- game winning streak stopped. Ryan Miller allowed all three goals on 31 shots in the loss.
Buffalo is on the outside of the playoff chase with 68 points, four back of Winnipeg.
"We weren't skating to our full as you can tell," said Miller. "I'm so tired from this trip, I can't even talk right now. But that's the difference, you've got to be smart and you've got to be patient."
With the score tied in the third, Winnipeg took a 2-1 lead 8:02 into the period. Little grabbed the puck in his own zone and sent a breakout pass to Wheeler, who grabbed the puck near mid-ice on a clean breakaway and buried his shot into the right corner.
"Little made a really heads up play," said Wheeler. "They turned it over inside our blue and their defenseman was going in on kind of a four on three rush and saw that I was free. I always feel fortunate scoring on a goalie like him. He's probably the best in the league right now and you got to take a little bit of luck out of that, but it felt good to win tonight."
Thorburn gave his team an insurance goal less than three minutes later when he took the puck through the middle of the neutral zone, cut to the right then back to the front behind his defender and slipped the puck in.
Pavelec turned aside all eight shots he faced in the third to give the Jets a big win.
Winnipeg got the only goal of the first period as Little's shot from the outside right circle was stopped, but the rebound popped into the air and Ladd was there to knock it home.
In the final minute of the second period, the Sabres tied the game when Tropp was able to jam home a rebound from the left side with 34.8 seconds showing.
Buffalo hosts Carolina on Wednesday...Winnipeg hits the road for the next two games in Vancouver and Calgary on Thursday and Friday...Winnipeg took three of four from Buffalo this season...Both teams went 0-for-2 on the power play.