The Mitchelton-Scott rider quickly distanced the other favourites after a devastating attack on the Cote de La Redoute and soloing to the win.
"We wanted to make it hard on the climbs," said van Vleuten. 'The team did an epic leadout into La Redoute, I was first onto the climb and that's where I put the hammer down.
"My words for today were ‘when I go, don’t look back, attack, commit and go’ and that's what I did!"
Van Vleuten has been a visibly frustrated figure at times during the 2019 Ardennes classics, clearly in very good form, but just finding one rider better at both Amstel Gold and Fleche Wallonne.
"I really wanted to win this one (Liege) this spring," said van Vleuten. "It was nice to start off with Strade Bianche, but to finish it off with Liege-Bastogne-Liege... it's so good after I was so close in the Ardennes this week."
A small bunch formed behind to chase but the Dutch star was able to gradually extend her lead. With van Vleuten's figure rapidly disappearing down the road, Elizabeth Deignan (Trek-Segafredo) attacked off from the chasing group.
Deignan was unable to gain much ground, and with Australian Amanda Spratt (Mitchelton-Scott) marking the chasing group, they fell further behind van Vleuten.
The gap continued to grow and atop the Cot aux Fachons the world time trial champion's advantage was a minute and twenty seconds to Deignan, who was joined by a bridging pair of Elisa Longo Borghini (Trek-Segafredo) and Annika Langvad (Boels-Dolmans).
Van Vleuten's gap continued to increase as she got closer to the finish, eventually winning with a commanding margin of a minute and 39 seconds.
The chasing trio was caught by the larger group behind and Floortje Mackaij (Team Sunweb) managed to get away and went over the line to take second.
Demi Vollering (Parkhotel Valkenberg) led a select group home in the reduced bunch sprint for third, with Australia's highest placed finisher Amanda Spratt in 11th.