The Dutchman, who now has five Monument titles to his name, produced a trademark brutal acceleration in the Koppenberg cobbled ascent, 45 kilometres from the finish, and never looked back as several riders had to step off their bikes.
The cycling calendar has five Monuments - Milan-Sanremo, the Tour of Flanders, Paris-Roubaix, Liege-Bastogne-Liege and the Giro di Lombardia.
Van der Poel, the eighth man to win a record three Tours of Flanders, also won Milan-Sanremo and Paris-Roubaix last year.
He will be the heavy favourite for the Flanders-Roubaix double when he rides in the 'Queen of the Classics' next Sunday.
Van der Poel, the first rider with five consecutive podium finishes on the Tour of Flanders, was in a class of his own in the Belgian rain in an event his rival, local favourite Wout van Aert, missed after sustaining injuries in the Dwars door Vlaanderen one-day race on Wednesday.
The warm-up race was won by Matteo Jorgenson but the American cracked as he was chasing Van der Poel after the Alpecin-Deceuninck rider's attack.
Van der Poel was in a world of his own and he crossed the line more than a minute ahead of Italian Luca Mozzato and Australian Michael Matthews after 270.8 kms.
Defending champion Tadej Pogacar did not take part in the race as he is focusing on a Giro d'Italia-Tour de France double this season.
