The 20-year-old Liquigas rider, in his first season in cycling's elite, attacked the peloton with France's Christophe Le Mevel less than two kilometers from the finish and held on until the finish to beat Italian Mirco Lorenzetto by two seconds.
Spain's Alejandro Valverde took third place to bag a four-second time bonus and narrow the gap on overall leader Alberto Contador to 20 seconds.
The twice Tour de France champion finished safe in the favorites' group although his Astana team had a rough day in southern France.
They never controlled the stage, with many riders trying their luck from the start, but Spaniard Contador stayed vigilant and went over to Sagan to congratulate him after the finish.
Sagan, who won Wednesday's third stage to Aurillac, fell on the grass in exhaustion after crossing the line.
It had briefly looked like an upset was on the cards when Reine Taaramae took advantage of a counter attack after Colombian Leonardo Duque broke away on his own, and the Estonian champion slipped into a group of four that built an 80-second lead.
Taaramae, who started the day 1:06 behind Contador, prompted the bunch to react with Astana leaving the Caisse d'Epargne and Lampre squads to lead the chase.
It was game over for the fugitives 22 km from the line but the bunch split in two when the AG2R La Mondiale team tried to catch the big guns off guard with a sudden acceleration shortly afterwards.
The decisive burst, however, came from Sagan, who had already marked himself out by dropping seven-times Tour de France champion Lance Armstrong in the Willunga climb during January's Tour Down Under.
