Jhonas Enroth stopped 36 shots and stayed 1.
Derek Roy netted a goal and two assists for the Sabres, who are winners of four straight. Enroth moved to 5-0-0 in six games.
Jordan Leopold, Ville Leino, Matt Ellis and Luke Adam also netted goals and Drew Stafford added three assists for Buffalo, which has defeated Ottawa six consecutive times.
Sergei Gonchar recorded the lone tally for the Senators, who are losers of five straight since its season-high, six-game winning stretch.
Craig Anderson started and let in two goals on six shots before being pulled in the first period. Alex Auld finished the game stopped 12-of-15 shots.