Strikers Dario Gandin and Andres Silvera scored either side of half time to take Independiente to 17 points from eight matches.
Gandin put the home side ahead in the "clasico" at the Libertadores de America stadium when he raced onto a fine chip forward by midfielder Walter Acevedo in the 38th minute.
Silvera exchanged passes with midfielder Walter Busse before netting the return from close range on the hour for his sixth goal, joining Martin Palermo of Boca Juniors as the championship's leading scorers.
The new leaders are two points ahead of Godoy Cruz, who lost the last remaining unbeaten record in the first division with a 2-1 defeat away to Newell's Old Boys in Rosario.
Uruguayan striker Joaquin Boghossian scored twice in 11 minutes as Newell's came from behind.
Newell's veteran defender Rolando Schiavi was dismissed after half an hour and Godoy Cruz midfielder Nicolas Olmedo followed four minutes later.
Title holders Banfield, winners of the Apertura in December, are third with 14 points after a 0-0 draw at Atletico Tucuman.
Velez Sarsfield, winners of last season's Clausura, lost ground with a 1-0 defeat at Argentinos Juniors and are equal on 12 points with Newell's and Colon, who visit Arsenal on Monday.
Boca Juniors, in the lower half of the table like their arch-rivals River Plate, were upset 2-1 at home by Racing Club on Friday.
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