Goaltender Robin Lehner made 38 for the Sabres (5-5-3), who had won their previous three road games.
Boston outshot Buffalo 42-32, including 15-5 in the second period.
Marchand opened the scoring with a power-play goal at 5:44 of the second period. His wrist shot went off Lehner's mask and stick before trickling behind the goalie for a 1-0 Boston lead.
After a double minor for high sticking to Zemgus Girgensons at 7:50 and two minors to Jake McCabe at 9:16, the Bruins took advantage of an extended 5-on-3 power play when Krejci scored at 10:12 of the second for a 2-0 lead.
"It gets you out of your rhythm," Sabres captain Brian Gionta said about their penalty troubles. "Obviously, it gives them momentum, but the biggest thing is you're over-taxing your killers and not getting a good rotation when the guys are sitting down."
Nash got a fortuitous bounce to score his first goal of the season and give Boston a 3-0 lead. Matt Beleskey pressured Buffalo defenseman Dmitry Kulikov, who blindly sent the puck up the wall, and Nash intercepted and sent it toward the net, where it deflected past Lehner off Kulikov's skate at 14:41.
Pastrnak scored on the power play at 9:45 of the third period for a 4-0 lead.