Van Vleuten, 36, attacked with 32km to go and no one could go with her as she built a commanding lead.
In the end the world time trial champion finished 1:39 and 1:43 respectively ahead of compatriots Floortje Mackaij and Demi Vollering.
Coming into the race Van Vleuten had finished second in consecutive races at the Amstel Gold and Fleche Wallone. Her victory means she leads the Women’s World Tour.
There was another encouraging display from Lizzie Deignan as she continues her return from giving birth.
Deignan chased hard to try and catch the eventual race winner but had to settle for seventh in the end.
Liège-Bastogne-Liège Femmes Results
1 Annemiek van Vleuten (Ned) Mitchelton-Scott Women 3:42:10
2 Floortje Mackaij (Ned) Team Sunweb Women 0:01:39
3 Demi Vollering (Ned) Parkhotel Valkenburg 0:01:43
4 Soraya Paladin (Ita) Ale Cipollini
5 Lucinda Brand (Ned) Team Sunweb Women
6 Katarzyna Niewiadoma (Pol) Canyon-SRAM
7 Elizabeth Deignan (GBr) Trek-Segafredo Women
8 Alena Amialiusik (Blr) Canyon-SRAM
9 Elisa Longo Borghini (Ita) Trek-Segafredo Women
10 Cecilie Uttrup Ludwig (Den) Bigla Pro Cycling Team