Penarol defeated Sud America 2-0 on Saturday to move above Fenix into first position in the table and when Danubio triumphed on Sunday, the title-holders were assured of top spot through 10 games.
Jonathan Alvez struck a brace for Danubio with the striker's second coming in the 79th minute to sink Fenix.
Penarol lead the league on 20 points, one point ahead of Wanderers - who thrashed Miramar Misiones 5-0 on Sunday - with Fenix (18 points) in third, ahead of Danubio on goal difference.
On Saturday, a stunning long-range effort from Carlos Nunez put Penarol ahead just three minutes into the second half.
Nunez cut inside from the left, wheeling around onto his right foot at the top of the box and then unleashing a rocket into the top corner of the net.
Luis Aguiar capped off Penarol's victory in the 86th minute, sliding in at the back post to tap in Marcelo Zalayeta's cross.
At Fenix's Parque Capurro on Sunday, Alvez struck in the 11th minute for Danubio, converting from Ignacio Gonzalez's pass but the home side were level at half-time through Lucas Cavallini.
Fenix dominated the match with 17 shots to five but Alvez clinched three points for the visitors with 11 minutes remaining.
The victory took Danubio up to 18 points but their goal difference of plus four sees them remain just behind Fenix (plus eight).
Rodrigo Pastorini struck a double for Wanderers in their demolition of bottom club Miramar Misiones with Diego Riolfo, Gaston Rodriguez and Nicolas Albarracin scoring the other goals, while in other fixtures on Sunday, Racing edged out Cerro Largo 1-0, Juventud defeated River Plate 3-1, Nacional trumped Defensor Sporting 2-0 and El Tanque Sisley won 3-1 at Cerro.
Liverpool defeated Rentistas 2-0 on Saturday.
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