A comeback win for the ages saw van der Poel drag a chase group back into contention before overtaking a cat-and-mouse game between Julien Alaphilippe (Deceuninck-QuickStep) and Jakob Fuglsang (Astana) to take a dramatic victory.
Clarke stuck himself on van der Poel's wheel and was the only one who could respond when the Dutch star launched his sprint, finishing second ahead of Fuglsang.
After an early break had established itself and been brought back gradually, it was up to the big names of the race to fight it out for the win at the Amstel Gold Race.
Van der Poel (Correndon Circus) kicked off the action among the favourites with a searing attack with 46 kilometres remaining in the race. His attack was too hard to follow for all except Gorka Izagirre (Astana). The main bunch responded and were able to bring the Brabantse Pijl winner back before he got out to a large gap.
Julien Alaphilippe (Deceuninck-QuickStep) launched what proved to be the decisive attack with 36 kilometres left to race, jumping away on the Fromberg. Matteo Trentin (Mitchelton-Scott) was the quickest to respond, but only Jakob Fuglsang (Astana) could bridge to the Frenchman, while Trentin settled in with Michael Woods (EF Education First), Peter Sagan (BORA-hansgrohe) to chase.
Sagan was dropped soon after, to be replaced by Michal Kwiatkowski (Team Sky) who bridged across.
The gap grew for the leading pair, stretching to a minute as the peloton's chase behind was hampered by riders trying to attack solo.
The Trentin chase group hovered between the peloton and the leading pair, and nearly made contact as the race went up the Cauberg for the final time with 20 kilometres remaining, before Fuglsang and Alaphilippe re-established their advantage.
With the race coming into the final kilometres, attacks continued to flow from the peloton with a number of small moves from Maximilian Schachman (BORA-Hansgrohe), Bauke Mollema (Trek-Segafredo) and Clarke made small inroads into the front two's lead.
Fuglsang began to attack Alaphilippe with seven kilometres remaining and failed to cooperate at all with the pace-making with three kilometres left to race. Alaphilippe began to soft-pedal in response as Kwiatkowski attacked from the chasing group took in lone pursuit.
Van der Poel, meanwhile, was driving the pace back in the remnants of the main bunch, gathering up riders who had previously attacked off the front.
As Alaphilippe led into the final kilometre, it became clear that Kwiatkowski was going to bridge to front of the race and maybe the chasing bunch would as well, as a charging van der Poel led them home.
Despite a spirited surge from Kwiatkowski, van der Poel's impressive sprint saw he and a slipstreaming Simon Clarke overtake the leaders, with the Dutch multi-discipline star able to take a famous victory.
