Michal Kwiatkowski (Omega Pharma-QuickStep) claimed the biggest one-day race victory of his career in Strade Bianche, distancing breakaway companion Peter Sagan (Cannondale) on the final climb to the finish with a blistering attack.
Alejandro Valverde (Movistar) rounded out the podium to take third place.
"I didn't expect to drop him," Kwiatkowski said after he crossed the line.
"I knew the final pretty well. As a team we were so good today, we had five riders in the front with 50km to go and we controlled the race. I can't describe how I feel. Winning in Siena is an amazing feeling.
"I didn't have any problems in the winter and was focused on my work. I started late compared to last year but I'm really happy with my condition."
Kwiatkowski and Sagan, clearly the two strongest riders in the race, broke clear with 21km remaining after a dangerous move including Cadel Evans (BMC) and Ian Stannard (Team Sky) was caught inside the final 30 kilometres.
Sagan, who was riding with little team support in the final 50 kilometres, was the first to attack, with Kwiatkowski the only one capable of bridging across to the Cannondale rider.
From there the pair set about building on an advantage that peaked at over one minute over the final three sections of gravel roads ahead of the finish in Siena.
Alejandro Valverde, Fabian Cancellara (Trek Factory Racing), Damiano Cunego (Lampre-Merida) and Roman Kreuziger (Tinkoff-Saxo), who all had no answer when the leading pair broke clear, formed a late chasing move but they were unable to reel back the two leaders.
Approaching the final climb, and with Sagan and Kwiatkowski working well together throughout their break, it was the Slovak champion who lead onto the final ascent with the gradient rising to over 16