Alvaro Gutierrez's men made it 14 wins in 15 matches with a 1-0 road victory over bottom-placed Tacuarembo.
Ivan Alonso's 15th goal of the Apertura phase saw him finish the first half of the season four goals clear atop the golden boot standings, and handed Nacional a 10-point buffer on second-placed Racing.
Nacional had already sealed the Apertura title, and spot in the championship play-off, in November.
Racing won 10 of 15 matches, coming from behind to win 3-2 at third-placed Penarol.
Penarol led 2-0 heading into the second half, after a fifth-minute strike from Damian Macaluso was followed by Jonathan Rodriguez's goal later in the half.
But a quick-fire Daniel Acosta brace - he scored in the 54th and 58th minutes - and Gabriel Fernandez's winner in the 67th minute saw Racing complete a whirlwind comeback.
Racing finished seven points clear of Penarol.
River Plate missed the chance to climb third, finishing fourth on goal difference behind Penarol after a 2-1 home loss to Danubio.
River finished with just nine men after two late dismissals, and Agustin Ale's late own goal saw them fail to usurp Penarol.
Fifth-placed El Tanque Sisley finished the Apertura phase with consecutive draws, being held at home to Atenas 0-0.
Defensor Sporting went sixth with a 2-0 home victory over Rampla Juniors, ahead of five sides level on 20 points.
Sud America (seventh, even goal difference) were the best of the bunch, as Juventud (minus one), Atenas (minus two), Danubio (minus three) and Rentistas (minus six) all had negative goal differences.
Sud America edged Wanderers - one point back in 12th - 1-0 to climb above their opponents.
Juventud also finished in winning fashion, thrashing Rentistas 3-0.
Fenix ended a five-match losing streak, trumping Cerro 3-1 on the road after conceding the opener.