The race was temporarily neutralised after the crash around the 198km mark, which left several riders injured, and forced Australian Jay Vine and Norwegian Adne Holter to abandon.
Spaniard Florian Stork finished second, and Giulio Ciccone was third, as XDS Astana rider Thomas Silva took the pink jersey from stage one winner Paul Magnier.
The stage started without Matteo Moschetti, who was caught up in a crash on Friday and became the first competitor to abandon the race.
Mirco Maestri and Diego Pablo Sevilla attacked early and moved five minutes ahead of the peloton. They remained unchallenged through the climbs to Byala Pass and Vratnik Pass, where Sevilla led the way to the top.
But the peloton slowly chipped away at the breakaway riders in rainy conditions, and once the weather cleared up, Maestri and Sevilla were caught with 27km left in the stage.
But the mass crash followed soon after.
Commentators said Marc Soler was the first to hit the ground that was still slippery from the rain, before several others got caught in the crash, with some hitting or going over a guard rail.
The race resumed with 18.2km left, and Jonas Vingegaard attacked during the Lyaskovets Monastery Pass, opening a gap with the peloton near the top as Giulio Pellizzari and Lenny Van Eetvelt chased him down the descent.
But with half a kilometre left, the peloton caught up with the leading group, leading to a frantic sprint in which the Uruguayan 24-year-old prevailed in a photo finish.
The race will continue on Sunday with a 175km flat stage from Plovdiv to Sofia.
