Pablo Lima's 80th-minute strike was enough to seal first position after River Plate's 1-1 draw at Defensor Sporting.
Lima's winner gave Danubio their fourth title and first since 2007, as they pinched the Apertura after River's draw and Nacional's loss.
River Plate equalised in the 86th minute through Sebastian Taborda, but were unable to find a title-winning goal.
Nicolas Olivera had put Defensor ahead on 67 minutes.
Nacional appeared to be headed for the title, needing a win at home to Fenix and taking the lead before suffering a 2-1 loss.
Fenix defender Leandro Zazpe scored an own goal to give Nacional the lead after 17 minutes before they fought back with second-half goals to Ignacio Pallas and Hernan Novick.
Despite Fernando Machado receiving a second yellow on 86 minutes, Fenix held on to deny Nacional.
In the standout individual performance of the round, Sergio Blanco scored four goals as Wanderers smashed El Tanque Sisley 5-0 despite possession being shared.
Blanco grabbed his first goal on 38 minutes before his other three came in an 11-minute period in the second half.
In other results, Cerro required two late goals to see off Liverpool 2-1 while there was a goalless draw between Miramar Misiones and Juventud.
Rentistas drew 1-1 with Racing while Cerro Largo saw off 10-man Penarol 1-0.
