Nacional sealed the title and qualified for the championship play-off - which pits the Apertura winner against the Clausura champions - last week after edging second-bottom Cerro 1-0 in round 13.
And the Montevideo club did not let up against Juventud at the Estadio Gran Parque Central on Saturday, recovering from a slow a start to win their 11th consecutive league match in the penultimate week.
Juventud - 11th in the standings - took a surprise 13th-minute lead when Rodrigo Viega headed across Nacional goalkeeper Gustavo Munua.
Nacional were back on level terms 14 minutes later, veteran striker Ivan Alonso tucking the ball underneath Martin Rodriguez.
And Alonso, 35, was at it again in the 34th minute, successfully converting a spot-kick for his 14th goal of the season.
Henry Gimenez headed Alvaro Recoba's cross into the far corner of the net eight minutes after half-time and substitute Gaston Pereiro completed the scoring with five minutes remaining.
Nearest rival Racing - 10 points adrift of Nacional - lost for the first time in four matches, beaten 2-0 at home by third-placed River Plate.
Goals to Cristian Techera and Jonathan Ramirez saw River bounce back from their 1-0 loss to El Tanque Sisley.
In other results, second-half goals from Jonathan Rodriguez and Marcelo Zalayeta helped fourth-placed Penarol overcome lowly Fenix 2-1 on Sunday.
Guillermo Maidana bagged a brace as Rentistas accounted for Cerro 3-1 and Diego Riolfo's 79th-minute strike gave Wanderers a 1-1 draw at home to Defensor Sporting.
Cellar-dwelling Tacuarembo earned a 1-1 draw with Rampla Juniors, Danubio and El Tanque Sisley drew by the same scoreline, while Atenas and Sud America played out a goalless stalemate.