Roman Kreuziger stunned race favourites Philippe Gilbert and Peter Sagan with a late solo attack to claim victory at the Amstel Gold Race.
The Czech Republic rider burst clear of the field on the penultimate climb, 7km from the finish line, and held on for the biggest one-day race win of his career.
World champion Gilbert launched a mammoth counter-attack on the final climb, the infamous Cauberg, but was unable to close the gap and had to settle for fifth in a reduced-bunch sprint.
Spain's Alejandro Valverde took second ahead of Australia's Simon Gerrans in third, but Sagan laboured up the Cauberg and finished well down the field.
Kreuziger said: "It was a big surprise, but the team was excellent and, at the end, also my legs. I am really happy to take the win.
"We saved a lot of energy and maybe this energy was what I needed at the end. On the final climb of Cauberg, I just looked down and pedalled without thinking so much. At the top I had about 20 seconds and I knew that I could do it."
The Amstel Gold Race is the first of three events within the space of eight days that make up the Ardennes Classics and this year's edition took place over 251.8km, starting in Maastricht and finishing in Valkenburg in the Netherlands.
A seven-man breakaway group opened up a gap of almost 11 minutes on the peloton, but with the race's 34 steep climbs taking their toll, their ranks were reduced to three with just over 53km remaining.
Spain's Mikel Astarloza (Euskaltel-Euskadi) later forged clear on his own, yet the real action was taking place behind him, where riders had begun attacking out of the peloton at will.
A chase group including Kreuziger (Saxo-Tinkoff), Pieter Weening (Orica-GreenEDGE), Andriy Grivko (Astana) and Damiano Caruso (Cannondale) formed and soon reeled Astarloza in, entering the final 10km seven-strong.
But then Kreuziger, who has won stage races including the Tour of Romandy before but never a Classic, sprang clear on the ascent of the Bemelerberg and was not seen again. He time-trialled his way to the foot of the Cauberg, negotiated the climb with a healthy advantage intact and crossed the line 22 seconds ahead of his nearest rival.
Back down the road, Gilbert (BMC) stormed up the last of four ascents of the Cauberg and took both Valverde (Movistar) and Gerrans (Orica-GreenEDGE) with him. The trio initially gave chase to Kreuziger on the subsequent 1.8km of flat to the finish line, but after giving up hopes of victory, they turned their attentions to a sprint for second.
The race had earlier been marred by a series of crashes as the peloton struggled its way through a tight and winding course.
France's Thomas Voeckler (Europcar) was taken to hospital with a suspected broken collarbone after crash 92km from home, while Spain's Joaquim Rodriguez (Katusha) saw his Ardennes Classics campaign put into jeopardy by a knee injury sustained in a fall 45km out.
The Ardennes Classics continue with La Fleche Wallonne on Wednesday and Liege-Bastogne-Liege next Sunday.
Watch two hours of highlights of the Amstel Gold Race on Sky Sports 4 from 7pm on Sunday, repeated at 1.30am and 2pm on Monday
1 Roman Kreuziger (Cze) Saxo-Tinkoff, 6:35.21
2 Alejandro Valverde (Spa) Movistar, +22secs
3 Simon Gerrans (Aus) Orica-GreenEDGE, st
4 Michal Kwiatkowski (Pol) Omega Pharma - Quick-Step, st
5 Philippe Gilbert (Bel) BMC, st
6 Sergio Henao (Col) Team Sky, st
7 Bjorn Leukemans (Swe) Vacansoleil-DCM, st
8 Pieter Weening (Ned) Orica-GreenEDGE, st
9 Enrico Gasparotto (Ita) Astana, st
10 Bauke Mollema (Ned) Blanco, st