Alexandre Burrows and Chris Higgins each had a goal and an assist for the Canucks, who went 3-1-1 on their 12-day trip. Jannik Hansen , Mason Raymond and Daniel Sedin also scored.
The Maple Leafs struggled against Vancouver's top line of Burrows, Henrik Sedin and Daniel Sedin, who returned to the lineup after sitting out Thursday's game in Carolina with back spasms. That unit accounted for the two most important goals of the game.
Burrows found Daniel Sedin with a perfect pass late in the second period to help Vancouver grab the lead. Burrows then scored himself with a nice wrist shot with less than six minutes remaining in the game, making it 4-2.
Phil Kessel scored his 19th goal to get Toronto within one, but the Leafs couldn't find the equalizer before Hansen iced it with a nice individual effort.
Joffrey Lupul and Tyler Bozak also scored for the Maple Leafs.
Even though Toronto was playing for the second straight night and Vancouver was wrapping up a five-game trip, two of the NHL's better-skating teams played at a high pace. The back-and-forth game featured quality scoring chances at both ends and excellent goaltending despite all of the scoring.
Higgins opened the scoring just 1:02 into the game after he was left alone in front on a blown coverage by Leafs defenseman Jake Gardiner. He beat Jonas Gustavsson high for his ninth goal of the season.
The Leafs responded quickly when Lupul went to the net and Bozak's shot hit him before he swept the puck in for a power-play goal at 3:58.
But the goalies were the real stars of the opening 20 minutes. Luongo heard chants of ''Luuuu!'' from the large cluster of Canucks fans at Air Canada Centre when he got his glove on a Colby Armstrong shot. Gustavsson then came across his crease to rob Burrows.
Another quick goal in the second period put Vancouver ahead 2-1. Raymond scored at 49 seconds for his third goal in six games since returning from the serious back injury he suffered during last year's Stanley Cup final.
Bozak tied it with a nice backhander off the rush at 7:33 before Daniel Sedin gave the Canucks the lead for good at 19:16, one-timing Burrows' pass over Gustavsson.
That allowed Vancouver to continue its dominance of the Leafs. The Canucks have won nine straight meetings between the teams dating to Nov. 24, 2003.
NOTES: The teams meet again Feb. 18 at Rogers Arena. ... Andrew Ebbett, Andrew Alberts and Alexander Sulzer sat out for Vancouver. ... The Leafs scratched David Steckel, Colton Orr and Jay Rosehill. ... Announced attendance was 19,633.