The home favourite struggled to escape for much of the 129-kilometre eight-lap race, but finally got clear on the intimidating Cauberg Hill to sprint to victory on the last two ascents.
With a finishing time of three hours 14 minutes and 29 seconds, Vos beat Rachel Neylan of Australia by 10 seconds, with Italy's Elisa Longo-Borghini third.
Dutch time trialist Ellen van Dijk was a notable casualty in a crash involving fifty riders on the second lap. Emma Pooley was the best-placed Briton, almost five minutes down in 15th place.
Olympic gold medallist Vos told limburg2012.nl: "It's been an amazing year. Really incredible. It started great with the Cyclocross World Championships but then I broke my collarbone.
"My plan was to get in shape at the Giro d'Italia. Well, that worked and I won. Then the gold at the Olympics, the World Cup and now this.
"I asked the girls to keep the gap at 35 seconds, you can bridge that on the Cauberg. It was pretty hard, especially the last 1.5km with a headwind."
Neylan added: "I wasn't surprised when Marianne caught up with us. As for Marianne's attack, I knew she wouldn't wait until the finish line."
Longo-Borghini, 21, said: "The best woman won today, she's been the best all year.
"I was always riding in the front of the group, keeping an eye on Marianne, so I wasn't involved in the crash.
"After the Cauberg I gave everything and this is the result. If you had told me two years ago I wouldn't have believed you."
Earlier today, Alexey Lutsenko became the new men's under-23 world champion.
The Kazakhstan rider beat Bryan Coquard of France, a silver medallist in the omnium at the London Olympics, with
Belgian Tom van Asbroeck taking bronze after a bunch sprint.