The Tinkoff rider, who broke a wheel early in the race, crossed the line 25 seconds ahead of Swiss Fabian Cancellara, who was aiming to become the first man to win the Belgian classic three times. Vanmarcke finished third.
"I’m really happy and of course the race was super hard from start to finish, it was full gas all day," said Sagan, who had exited his team bus before the race with the Star Wars theme music playing in the background.
"I want to dedicate this title to the two guys who died last week," he added.
Belgian Antoine Demoitie died following an accident involving a motorbike during the Gent-Wevelgem race last Sunday. His compatriot Daan Myngheer died on Monday after suffering a heart attack in the Criterium International.
Sagan and Michal Kwiatkowski made a decisive move with about 40 kilometres left in Sunday's 255-km race when they pulled away from the main pack and were quickly joined by Vanmarcke.
Cancellara decided to remain in the peloton along with defending champion Alexander Kristoff, trusting his ability to close the gap later on in the race.
Sagan, however, did not wilt, while Cancellara had nobody to work with as he made his move to catch the world champion some 23 kilometres from the line. Pre-race favourites Arnaud Demare of France and Belgian Greg van Avermaet crashed out early on.
After the Milan-San Remo, the Tour of Flanders was the second of the season's 'Monument' races, the name given to cycling's five most revered one-day classics.
It will be followed next Sunday by the Paris-Roubaix, dubbed the ‘Queen of the Classics’, the Liege-Bastogne-Liege race later this month and the Tour of Lombardy in October.
(Reporting by Julien Pretot; Editing by Toby Davis)
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