It was Luongo's 63rd career shutout and came in his 754th appearance for the Canucks over 14 seasons.
The Sabres -- who have just one victory in their first nine games this season -- were shut out for the second time this season and have scored just once in five other games.
They were coming off their lone win of the season, a shootout decision over the New York Islanders on Tuesday.
Vancouver scored once in each period , the first goal coming from Chris Higgins with 5:07 to go in the opening stanza.
Brad Richardson had a shorthanded goal in the second period and Ryan Stanton tallied midway through the third.
Ryan Miller allowed all three goals on 34 shots.