Independiente started the Copa Libertadores campaign with a 2-0 home win over Ecuador's Deportivo Quito in the first leg of the first stage on Tuesday.
The Argentinian giants, who have won the Copa Libertadores seven times, were held in the opening half but eventually triumphed after the break thanks to goals by debutant Matias Defederico and Patricio Rodriguez.
Defederico, on loan from Brazilian giants Corinthians, put the Red Devils ahead five minutes after the interval with a left-foot strike after a mistake by Deportivo Quito defender Luis Checa.
Independiente were not playing good football at the Estadio Libertadores de America, but 20 minutes after the opener Rodriguez connected with a Nicolas Cabrera free-kick to double the advantage.
The second leg will be played next Tuesday in Quito, at 2,800 metres above sea level so Independiente will face a difficult task if they are to make the group stage.
Independiente defender Eduardo Tuzzio said: "The result is enough only to think the second leg will be very tough. We'll play like if we had drawn 0-0 here. "The first half was difficult, even, but in the second we controlled the ball quite well. We should keep clean sheet in Quito."
Deportivo Quito forward Luis Fernando Saritama added: "We must be intelligent to clinch the qualification."
The winners of this tie will play in group eight alongside Uruguayan giants Penarol, Argentina's Godoy Cruz and Liga Deportiva Universitaria of Ecuador.