The home side took the lead in the 5th minute at the Silesian Stadium in the southern Polish city of Chorzów with a brilliant solo goal from winger Kamil Jóźwiak.
Memphis Depay equalized for the Netherlands after converting a penalty in the 77th minute.
Georginio Wijnaldum made it 2-1 for the Netherlands with a header seven minutes later.
Poland, captained by star striker Robert Lewandowski, had been looking to make amends for their bitter 0-2 defeat against Italy three days earlier, but failed to stop the Dutch side from dominating and ended 2020 on a low note.
Poland are ranked 18th worldwide by football's governing body FIFA, while the Netherlands are No. 15 in the FIFA table.
The Poles finished third in their Nations League Group A1, with seven points from six rounds of fixtures, five behind Italy and four less than the Netherlands.
In their previous Nations League games, the Poles beat 10-man Bosnia-and-Herzegovina 3-0 at home on October 10, tied 0-0 with Italy at home on October 11, beat Bosnia-and-Herzegovina 2-1 away on September 7, and lost 0-1 to the Netherlands away on September 4.
Italy on Wednesday night beat the already eliminated Bosnia-and-Herzegovina 2-0 in their last Nations League group-stage fixture and advanced to the competition's final four next year.
The Nations League is the European football governing body UEFA’s newest national-team competition that is now in its second edition.
The competition is designed to enable teams to play against those that are similarly ranked and also offers an alternative path for teams to qualify for the 2022 World Cup.
Portugal won the first edition of the Nations League last year.
Source: TVP Sport, PAP