Olympic road race champion Van der Breggen attacked with 7km, and one daunting climb up Cauberg, left and finished 55 seconds clear in her home race.
Deignan was in a chasing pack of five at the business end of the 121km route and came out on top in a bunch sprint for the line.
Amstel Gold Race
Gilbert beats Kwiatkowski to win Amstel Gold Race
There was a rare tie for third behind her, as Orica Scott's Annemiek van Vleuten and WM3's Katarzyna Niewiadoma could not be separated.
Deignan, a former UCI Women's World Tour champion, is up from 14th to seventh in the overall standings, with American Team Sunweb rider Coryn Rivera leading with 375.
The Amstel Gold Race was last seen in 2003, when Briton Nicole Cooke won.