The South American giants have gone to the second tier following three poor seasons in Argentina's top flight, with a 1-0 defeat to San Lorenzo confirming their demise
A lone goal by San Lorenzo's Angel Correa at Estadio Libertadores condemned Miguel Brindisi's men to their unenviable milestone, despite still having one round to play.
The record seven-time Copa Libertadores winners make the drop after being one of three teams to average the lowest points recorded over the last three campaigns.
First institutionalised in 1983 in an attempt to save River Plate from relegation, Argentina's Primera Division averaging system ensures Independiente will join Union in the Primera B Nacional next season.
San Martin and Argentinos Juniors will fight out to avoid the remaining relegation spot.
The Buenos Aires team had been recognised alongside Boca Juniors as one of the teams never to have been relegated in the Primera Division history.
Sergio Aguero, Gabriel Milito, Diego Forlan and Esteban Cambiasso are some of the illustrious names to have turned out for the Rojo before coming to European football.