It is the first time the Bruins have claimed the Presidents' Trophy since the 1989-90 season.
Cody Hodgson scored for Buffalo.
Sabres goalie Matt Hackett was taken from the ice on a stretcher after Boston defenceman Torey Krug fell on his right leg with 11:35 left. He was replaced by Connor Knapp, who allowed Krejci's second goal one minute later.
It is the second time the Bruins have won the Presidents' Trophy, given to the NHL team with the most regular-season points, since the award was instituted for the 1985-86 season.
FLYERS 4, PENGUINS 3, OT
Streit's backhand shot from the right circle caromed between Fleury's pads and into the net as the Flyers clinched third place in the Metropolitan Division.
Jakub Voracek scored twice for the Flyers, and Claude Giroux added his team-high 28th goal of the season. Ray Emery made 12 saves after replacing injured starter Steve Mason to start the third period.
Letang scored in the final minute of regulation to force overtime after Giroux gave the Flyers a 3-2 lead with 1:15 left.