Nestor Silvera scored the first goal at the Libertadores de America stadium, named after Independiente's record seven South American club titles and erected in the same place as the old ground built in 1928, before Ignacio Piatti added two more.
Silvera put Argentina's Red Devils ahead in the 12th minute from Piatti's lay-off, but Federico Nieto equalised in the 35th for his seventh goal of the season.
By the time of Independiente's third, Colon striker and captain Esteban Fuertes had been sent off for elbowing. Midfielder Alfredo Ramirez pulled another goal back in the 89th minute.
Racing, whose 1-0 loss away to Newell's Old Boys on Tuesday left them joint bottom with five points, no wins and in serious danger of relegation, were looking closer to home for a new coach, approaching Uruguayan Sergio Markarian.
Banfield, who won 1-0 at Gimnasia-La Plata on Wednesday with a 10th goal for Uruguayan striker Santiago Silva, the championship's top scorer, are second.
"We're still dreaming. We won at a very tough ground...Now we face a very difficult rival in what I think will be the most important match of the next round," said Silva referring to Banfield's home game with Estudiantes at the weekend.
Newell's are third, also on 23 points, while Diego Simeone's San Lorenzo are fourth with 22 points after twice coming from behind to beat Arsenal 3-2.
