The course started in Lucca near the coast and ended with 10 laps of a difficult 16.6-kilometer (10.3-mile) circuit in and around Florence.
For more than six hours, riders raced through heavy rain. But the sun eventually came out and dried the course for the final lap.
The circuit's highlights were one long climb, a 4.4-kilometer (2.7-mile) ascent to the scenic town of Fiesole with an average gradient of 5 percent, then after a brief but technical descent another short but steep climb of 600 meters (yards) with gradients as high as 16 percent.
With the constant climbing and descending, some riders compared it to a rollercoaster.
Despite the rain, fans turned out in large numbers, especially when riders passed by Florence's Duomo cathedral and wound their way through the city's medieval streets. There were also big crowds on the climbs.
Five riders broke away from the pack soon after the start and established a lead of 7 minutes at one point. But the main pack began to pick up the pace as it entered the circuit and of the original five Bartosz Huzarski (Poland), Rafaa Chtioui (Tunisia), Yonder Godoy (Venezuela), Matthias Brandle (Austria) and Jan Barta (Czech Republic) only Barta and Huzarski were left in front after five laps.
Huzarski was the lone leader when Italy's Giovanni Visconti caught up with him during the eighth lap.
Italy set the pace for the first few laps of the circuit, then Belgium took over and caught the leaders in the penultimate lap.
A pack of about 50 riders was in the lead entering the final lap. Then the attacks began, first by Italy's Michele Scarponi on the Fiesole climb, then by Nibali, and finally with Rodriguez and Rui Costa.
Pre-race favorites Peter Sagan and Fabian Cancellara couldn't respond to Scarponi's attack and were left behind.
With riders not permitted to wear two-way radios, they were advised of their status by team helpers along the side of the road holding up info boards, like in Formula One.
There were several crashes. One, on the second lap of the circuit, forced 2009 winner Cadel Evans of Australia to withdraw. On the final lap, Rigoberto Uran of Colombia crashed hard.
It was a race to forget for what was considered a strong British team featuring the last two Tour de France winners, Bradley Wiggins and Chris Froome, plus sprinting standout Mark Cavendish.
Of the eight British starters, none finished.
"Bad day for me today," Froome tweeted. "Really tough circuit under these conditions."
Also, it was announced that Jonathan Tiernan-Locke, who withdrew from the British team earlier this week, was notified by the UCI of a potential discrepancy in his biological passport data.
Next year's worlds will be held in Ponferrada, Spain.
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