The reigning world champion continued her superb record atop the Mur de Huy, taking out the win after an attacking race had seen plenty of action on the climbs and in the crosswinds.
Overtaking late escapee Floortje Mackaij (Team Sunweb) midway up the climb, it was Amstel Gold winner Niewiadoma who launched from the peloton first. Van der Breggen was able to overhaul her with 200 metres to go with Van Vleuten also passing the Polish star and challenging for the win.
Van der Breggen held on for the win, an important one for the normally dominant squad who have been a bit quiet so far this season.
"That big victory was not there yet, neither for me nor for the team," van der Breggen said. "So, it's good for all of us to have a big victory now. It's nice to win again. You don't really think about the previous years during the race, five years in a row, it makes me feel a bit old."
"The race is different every year, but the finish is always on top of the Mur and the second-last climb is also really hard, so it is always a hard final, and I think that suits me.
"Today, there were attacks, but we did not go full, so we came to the Mur with quite a big group. And that is difficult. You feel the pressure of going hard to follow other girls, but you cannot go too early because then you blow up.
"It is my fifth win, by now I know how to ride it and to pace it. You start it with heart rate 185 already, so it is difficult, but you have to wait until you really give it all, if you do it too early, then you don't win. I just tried to do my best today, and luckily it was enough."
It was a hard fought battle to establish the early breakaway with the move eventually forming after 30 kilometres of racing. Malgorzata Jasinska (Movistar Team), Diana Peñuela (Alé Cipollini), Lauren Stephens (Tibco-Silicon Valley Bank), Loes Adegeest (Parkhotel Valkenburg), Tatiana Riabchenko (Doltcini-Van Eyck), and Marie-Soleil Blais (Astana Women’s Team) got out to a maximum advantage of two and half minutes as they crested the Côte de Wârre, the first major climb of the day.
The break was brought back to heel and on the first ascent of the Mur de Huy, there was little action as the peloton kept a steady pace.
Jeanne Korevaar (CCC-Liv), Elisa Balsamo (Valcar Cylance), Ruth Winder (Trek-Segafredo), and Olga Shekel (Astana Women's Team) launched an attack with 22 kilometres left to race and started the Côte d’Ereffe 20 seconds ahead of the chasing peloton. They maintained the gap on the climb but were caught on the following descent.
Alison Jackson (Tibco-Silicon Valley Bank) attacked with 10km to go, but the Canadian was reeled in on the penultimate climb of the Côte de Cherave.
Niewiadoma attacked for the first time, which led to a group of 13 riders containing most of the pre-race favourites going clear of the bunch. Amanda Spratt (Mitchelton-Scott) was the next to attack over the top of the Cote de Cherave but was caught on the descent.
Mackaij launched the final move before the Mur, slipping away with less than three kilometres to go and obtaining a gap of 15 seconds. She led the race onto the final kilometre up the Mur de Huy but ultimately could not hold off the strongest riders.
Van der Breggen passed Mackaij with about 500 metres to go, then Niewiadoma made her move and took the lead. Relying on her experience on the infamous climb, van der Breggen waited until the final 200 metres where she passed Niewiadoma and rode to her fifth consecutive Flèche Wallonne victory.
Brodie Chapman (TIBCO-SVB) was the top-finishing Australian in ninth, with the aggressive Spratt in 11th and fellow Aussies Shara Gillow (FDJ-Aquitaine Futuroscope) and Rachel Neylan (Team Virtu) in the top 20.