The Team Sky man broke away from a leading group of four with 12km to go and managed to establish a maximum gap of 30 seconds over Greg Van Avermaet (BMC Racing), Tim Wellens (Lotto-Soudal) and Zdenek Stybar (Quick-Step Floors).
Once he was away on the final sector of gravel, there looked no stopping the 2014 Strade Bianche winner as the three behind struggle to pull together to close him down.
He crested the final climb to Siena's square to take caution around the wet corners after rain had battered the race through much of the day, and took time to celebrate as he rolled towards the line; his first victory since E3 Harelbeke last year.
Behind, Van Avermaet was able to continue his strong run of one-day results, taking second ahead of Wellens in third and Stybar further back in fourth.
How it happened
Jose Gonçalves (Katusha), Thibaut Pinot (FDJ), Simone Andreeta (Bardiani), Truis Engen Korsaeth (Astana) and Quentin Jauregui (Ag2r La Mondiale) formed the main breakaway of the day, getting away relatively early on in the day.
But they were never able to get much more than three minutes in the relatively short one-day race with several chase groups developing within the final 100km that quickly closed them down.
Andreeta was the first to call time from the break, and was quickly dropped approaching the closing 50km. The others ploughed on, but several attacks from big name riders behind had started to see a major chase group form that sat only 20-30 seconds behind them right into the final 40km.
The main chase group behind swelled to 12 riders, with the likes of Van Avermaet, Kwiatkowski (Team Sky), Wellens and Tiesj Benoot (Lotto-Soudal), Stybar, Edvald Boasson Hagen and Scott Thwaites (Dimension Data) and Tom Dumoulin (Sunweb) among them.
Kwiatkowski showed strength throughout the day particularly working to bring the break back, and the catch was eventually made at around 35km to go.
Despite Dumoulin also looking strong, he and most of the others that had managed to grab on to the lead group could do nothing to stay with Kwiatkowski, Van Avermaet, Stybar and Wellens when they went clear shortly after 25km remaining.
Orica-Scott pair Chris Juul-Jensen and Luke Durbridge made big efforts to try and bring the foursome back, but the situation remained the same and allowed Kwiatkowski to make his race winning move, adding a second victory to his 2014 win at Strade Bianche.
Strade Bianche 2017 (175km)
1. Michal Kwiatkowski (Pol) Team Sky, in 4-42-42
2. Greg Van Avermaet (Bel) BMC, at 15s
3. Tim Wellens (Bel) Lotto-Soudal, at 17s
4. Zdenek Stybar (Cze) Quick-Step Floors, at 23s
5. Tom Dumoulin (Ned) Sunweb, at 1-26
6. Luke Durbridge (Aus) Orica-Scott, st
7. Chris Juul-Jensen (Den) Orica-Scott, at 1-29
8. Tiesj Benoot (Bel) Lotto-Soudal, at 2-20
9. Thibaut Pinot (Fra) FDJ, at 2-23
10. Scott Thwaites (GBr) Dimension Data, at 2-52
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