Poland's Kwiatkowski outsprinted Spain’s Alejandro Valverde and Australia’s Michael Matthews to give his Etixx-QuickStep team a much needed win after a string of near-misses during the spring classics campaign.
Matthews, of Orica-GreenEdge, looked a solid bet for the win after following defending champion Philippe Gilbert (BMC) up the fourth and final ascent of the famous Cauberg climb.
But a leading group of around 20 riders came together on the 1.8km run into the finish before Kwiatkowski surged clear to pick up the first road win of his season - and get the rainbow-coloured monkey off his back.
Former world champion Rui Costa (Lampre-Merida) of Portugal finished fourth while Frenchman Tony Gallopin (Lotto Soudal) secured fifth place ahead of Belgian Greg van Avermaet (BMC).
SIX-MAN BREAK: Laurens De Vreese (Astana), Jan Polanc (Lampre), Timo Roosen (LottoNL-Jumbo), Linus Gerdemann (Cult Energy), Johann Van Van Zyl (MTN-Qhubeka) and Mike Terpstra (Team Roompot) formed the day's main break inside the first 40km of the 258km race.
The sextet built up a maximum lead of over 10 minutes as they grappled with the succession of 34 climbs that make the Amstel Gold Race in the Netherlands one of the most difficult of the spring classics calendar.
With the likes of BMC, Orica-GreenEdge and Movistar leading the chase, the lead came tumbling down towards the business end of the opening race of the Ardennes week.
COUNTER ATTACKS: With 38km remaining, the Eyserbosweg climb proved a pivotal moment as De Vreese, Polanc and Gerdemann shed their fellow escapees and rode clear.
Back in the peloton, Australians David Tanner (IAM Cycling) and Simon Clarke (Orica-GreenEdge) jumped clear to spark a response from Italy’s Vincenzo Nibali (Astana) and German time trial specialist Tony Martin (Etixx-QuickStep).
Tanner and Clarke joined De Vreese and Polanc in the lead while a six-man chasing group formed around Nibali, the Tour de France champion, and Martin.
Both Nibali and Martin - along with Alex Howes (Cannondale-Garmin) - joined the leaders after fellow chasers Diego Rosa (Astana) and Damiano Caruso (BMC) crashed out on a tight bend.
Another chaser - Dutchman Wilco Kelderman (LottoNL-Jumbo) - rode off the road and into a ploughed field after overcooking a bend.
The new five-man leading group had 45 seconds to play with over the peloton before Howes was the first to be caught, on the third of four ascents of the Cauberg around 20km from the finish.
Tanner soon followed suit, before Nibali and Martin appeared to take their foot off the gas - allowing Clarke to ride clear on the front of the race. The Australian had but a handful of seconds to play with and was caught before the theatrics of the penultimate climb of the day, the Bemeleberg.
Jakob Fuglsang (Astana) and van Avermaet broke clear for a few kilometres but the pair were gobbled up after BMC’s Belgian rider refused to pull.
CAUBERG DRAMA: In a bid to repeat last year’s result and launch Gilbert to a fourth Amstel Gold win, BMC sent Ben Hermans up the road at the start of the fan-thronged climb.
True to the script, Gilbert then leapt out of the saddle and tore clear - taking Matthews with him but distancing both Kwiatkowski and Valverde.
In hindsight, Matthews may regret having followed Gilbert’s wheel. For the race came back together over the summit with a group of around 20 riders - including former winners Enrico Gasparotto (Wanty - Groupe Goubert) and Roman Kreuziger (Tinkoff-Saxo) - reforming ahead of the finish.
Norway’s Lars Petter Nordhaug (Team Sky) led out the sprint with 300m remaining but Kwiatkowski proved the strongest despite a late wobble as the Polish 24-year-old looked behind before raising his arms aloft.
Veteran Valverde - for whom Amstel Gold remains the only of the Ardennes events whose podium top step he has yet to grace - settled for second place ahead of a tired Matthews. Gilbert, despite his best attempts on the Cauberg, came home in tenth.
It was Kwiatkowski’s second win of the season following victory in the Paris-Nice prologue last month - and his team's first major scalp since Zdenek Stybar won Strade Bianche in early March.
The Ardennes week continues with the Fleche Wallonne on Wednesday and Liege-Bastogne-Liege next Sunday.