Atletico Mineiro have won the Copa Libertadores once before in 2013, while America have reached the final on four separate occasions without ever lifting it.
Match preview
Atletico Mineiro, who finished third in last season's Brazilian top-flight, claimed a 1-1 draw at Venezuelan outfit Deportivo La Guaira last week to open their Copa Libertadores campaign.
Luis Martinez provided the hosts with a first-half lead, with Matias Zaracho's strike after the hour mark ensuring a share of the spoils.
However, given that his side had 72% possession and 29 shots across the 90 minutes, former Brazil international Cuca would have been disappointed not to see his side claim an away win which few would have argued with on the balance of play.
The 57-year-old, who guided Atletico Mineiro to their only ever Copa Libertadores triumph in 2013, was re-appointed for his second spell in charge of the club last month.
He will be hoping the likes of Eduardo Vargas and Hulk can help lightning strike twice for him, with a win against America on Tuesday taking them a step closer to the knockout stages.
America de Cali, meanwhile, began their campaign in disappointing fashion, losing 2-0 at home to Paraguayan outfit Cerro Porteno.
In a clash of the Colombian and Paraguayan champions, it was the latter who came out on top via strikes from Robert Morales and Angel Cardozo either side of half-time.
America dominated possession but struggled to convert their superior time on the ball into clear cut chances, testing opposition goalkeeper Jean on only two occasions in the entire match.
Francisco Arce, who played 61 times for the Paraguay national team during his playing career and has now won his country's top-flight twice with Cerro Porteno has a manager, will be demanding a much better performance from his players against Atletico Mineiro on Tuesday, otherwise they will be staring down an early exit from the Copa Libertadores.
Atletico Mineiro Copa Libertadores form:
Atletico Mineiro form (all competitions):
America de Cali Copa Libertadores form:
America de Cali form (all competitions):
Team News
Atletico Mineiro were without Diego Tardelli, Jair and Alan Franco through injury in last week's draw against Deportivo La Guaira, but Franco returned to the side in Saturday's win against Athletic, so could be involved.
Hulk only featured from the bench in his side's opening Copa Libertadores affair, but may start on Tuesday having gained further match fitness against Athletic.
America, meanwhile, are likely to travel without Steven Lucumi and Adrien Ramos after both missed last week's defeat to Cerro Porteno through injury.
Yesus Cabrera had a lively cameo having been brought on at half-time against Millonarios on Saturday, scoring before being sent off, but domestic suspension rules do not carry over so he should start in midfield here.
Atletico Mineiro possible starting lineup:
Everson; Guga, Rever, Alonso, Arana; Fernandez, Franco, Allan; Hulk, Vargas, Keno
America de Cali possible starting lineup:
Graterol; Arrieta, Torres, Murillo, Cabezas; Carrascal, Paz, Cabrera; Moreno, Mosquera, Vergara
We say: Atletico Mineiro 2-0 America de Cali
We expect the hosts to be too strong for the visitors here, with a defeat leaving the Colombian outfit facing an uphill task in terms of reaching the knockout stage.
The Brazilian side undoubtedly possess greater individual quality, with the likes of Vargas, Hulk and former Liverpool midfielder Allan Rodrigues de Souza capable of taking the game away from their opponents.