The Colombian, who was the best young rider in the Giro d'Italia, took his second victory of the year after a solo attack.
Matthew Lloyd (Lampre), Carlos Quintero (Colombia Coldeportes) and Oleg Berdos (Utensilnord-Named) formed the escape of the day on the 188km trek from Cuneo to Biella.
They built up a maximum lead of seven minutes over the largely flat first 150km but their advantage was under two minutes when they crossed the finish line for the first time at Piazza Vittorio Veneto in Biella with 34km to go.
The trio were soon caught on the first of two laps of a 16.8km circuit before the decisive selection was made on the second ascent of the 6.1km Favaro climb with an average gradient of 5.4% and some sections at 11%.
Uran, Luca Paolini (Katusha), Mauro Santambrogio (BMC) and Carlos Betancur (Acqua & Sapone) made the first move and were followed by Uran's compatriot and team-mate Sergio Henao plus Gorka Verdugo (Euskaltel-Euskadi).
The summit came with just 8km remaining and it was Uran who had the power to break away from the lead group on the run-in to the line, finishing comfortably ahead of Paolini and Verdugo.
“I’m very happy with the win today and I felt really good during the race," he said.
"Along with Sergio we tried to attack on the final lap before the finish. I was able to get away with Verdugo over the top of the climb but we did not have a big gap to the riders behind. We managed to stay clear and we gave it everything on the descent back to the finish.
He will look to maintain his form into Saturday's Il Lombardia, the final 'Monument' of the European cycling season.
“I have come out of the Vuelta with some really good fitness. The World Championships was some good preparation looking ahead towards Lombardy and today was also another really good warm-up. I really like the race and I and very motivated for Saturday,” he added.