The Pumas outscored Uruguay by eight tries to two after being 12-7 up at halftime.
Argentina were awarded a penalty try in the second minute and saw Uruguay’s Mateo Sanguinetti sent to the sin bin but did not take advantage of the numerical advantage, with Uruguay instead level after Felipe Aliaga went over in the 15th minute.
But a try for Mathais Moroni on the stroke of halftime put Argentina back ahead and after the break Julian Montoya, Santiago Cordero, Justo Piccardo, Rodrigo Isgro, Agustin Moyano and Nicolas Roger scored while Uruguay dotted down a second try through Ignacio Alvarez.
Argentina, who played the last half hour down to 14 after Pedro Rubiolo was red carded, are unbeaten in tests against Uruguay, having beaten them 79-5 when they met last year at Punta del Este.