Nacional secured Uruguay's Apertura championship title on Sunday after Alvaro Recoba scored 11 minutes from time to give them a 1-0 win over Liverpool.
Nacional, in Argentine Marcelo Gallardo's debut season as coach, will play for the overall title against the winners of the Clausura championship in the second half of the season.
Former River Plate, Monaco and Argentina midfielder Gallardo took charge in mid-year having hung up his boots as a Nacional player last season.
Penarol and Danubio both had a chance to win the title but Nacional's victory left Danubio, 4-1 winners over Bella Vista with a Diego Perrone hat-trick, a point behind in second place.
Penarol began the day a point above Nacional after their 5-0 rout of Cerrito on Saturday but they finished third, two points behind.
Recoba, who spent 11 years in Italy mostly at Inter, joined Nacional from Danubio this season.