Ashleigh Moolman-Pasio (Cervelo-Bigla) came in second, while Megan Guarnier (Boels Dolmans) took the bottom step of the podium after 118.8km from Huyn to Mur de Huy.
"I always hated this race," van der Breggen said. "Because the Mur is not nice to do, I mean it's really hard. But in fact, I started to love it more and more.
"It 's a hard race and it' s painful, but I try to enjoy it more and see the good things about it. And it makes a good race, it’s exciting. Especially how they made the circuit this year, it’s really beautiful. It’s not comparable to any other race.”
The race unfolded under a blazing sun, with temperatures hitting 25ִ degrees. Team Virtu Cycling's Doris Schweizer, a two-time Swiss time trial champion, broke away 30km into the race.
The bunch covered 39km in the first hour despite the hilly course. After 50km of racing, a four-woman group consisting of Ane Santesteban (Ale Cipollini), Omer Shapira (Cylance), Teresa Medvedova (BePink) and Dalia Muccioli (Valcar PBM) shot out of the peloton in pursuit of the lone breakaway.
The quartet managed to close down the gap, but the entire breakaway was reeled in at the foot of the first ascent of the Côte de Cherave at 83.5km.
Pauline Ferrand-Prévot (Canyon//SRAM) seized the opportunity to attack. The French rider's move resulted in a group of about 30 women breaking away from the peloton.
A while later, another attack from the French world champion thinned down the leading group to just four women with a handful of seconds on the rest of the peloton.
Ferrand-Prévot, Megan Guarnier (Boels Dolmans), Amanda Spratt (Mitchelton Scott) and Jenneke Ensing (Ale Cipollini) crowned the Mur de Huy for the first time with 45 seconds to spare over the other favourites.
However, their adventure came to an end a few hundred metres before the second and last ascent of the Mur de Huy, where van der Breggen again proved her dominance of the race.
"The tactics started earlier this year because of the altered course, that's why this group got away," van der Breggen said. "It was really good to have Megan there. It was a good situation for us, we didn’t do anything in the back and Megan tried to save energy in the break. I hoped the group would stick.”
"Megan had already done some 30 kilometres up front and you know that's already in her legs. So she did a great job to finish third. When Ashleigh accelerated, she appeared very strong today. I tried to follow her and hoped I had something left in the final sprint.”