The Penguins will have home-ice advantage in the opening round of the Eastern Conference playoffs when they take on Philadelphia. The teams will meet in their regular-season finale Saturday in Pittsburgh.
Fleury made 35 saves and won for the 226th time in his career. That equals the club record held by Tom Barrasso.
It was a 1-1 contest before Pittsburgh ran off three straight goals to take control. Tyler Kennedy put the Penguins in front to stay 8:27 into the contest, Richard Park produced the only second-period goal and Evgeni Malkin made it 4-1 midway through the third.
The Rangers will be the No. 1 seed in the Eastern Conference, but the loss put their bid to own the best record in the NHL in jeopardy. New York went into the game tied with Vancouver for the most points in the league at 109.
New York's Martin Biron played in his 500th career game and made 27 saves.