Flamengo can advance even if it loses to America at Maracana by 2-0 or 3-1. The five-time Brazilian champion is boosted by a 3-1 victory over rival Botafogo in the Rio de Janeiro state championship final on Sunday, when it earned its record 30th regional title.
It will be Flamengo's last match with manager Joel Santana, who is leaving to take over the South African national team. Caio Jr. was announced as his replacement on Monday.
The Brazilians were eliminated by local rival Sao Paulo the last time they reached the quarterfinals, in 1993.
America's first-leg loss prompted the resignation of Argentine coach Ruben Omar Romano, and the team will be commanded in Brazil by Juan Antonio Luna.
America is coming off a 1-0 victory over Monterrey in the Mexican league, a result that snapped its 12-match winless streak. It also was America's first win in six matches.
Argentina's Boca Juniors, seeking a seventh Copa Libertadores title, defeated Brazil's Cruzeiro 2-1 in Buenos Aires and needs a draw in Belo Horizonte on Wednesday.
Boca Juniors is coming off a 1-0 win over rival River Plate in the Argentine league, while Cruzeiro - a two-time Copa Libertadores champion - defeated rival Atletico Mineiro by the same score on Sunday to clinch the Minas Gerais state title.
Fluminense, which had the competition's best record in the group stage, defeated Atletico Nacional 2-1 last week in Colombia and another draw on Tuesday will be enough to get the Brazilian club through to the next stage for the first time in history.
"We have a good advantage and we need to use it," Fluminense goalkeeper Fernando Henrique said. "But we haven't won anything yet. The game in Medellin showed Atletico has a dangerous team. We'll need to be cautions in order to advance."
Atletico Nacional will be without injured Paraguayan striker Carlos Villagra and suspended goalkeeper David Ospina, who was ejected in the first leg.
Mexico's Atlas picked up a 1-0 over Lanus in Argentina and a draw also will be enough at home on Tuesday.
Also Tuesday, Ecuador's Liga de Quito will travel to Argentina to face Estudiantes and try to defend it 2-0 first-leg victory.
Two-time Copa Libertadores champion Santos also earned a 2-0 victory against Colombia's Cucuta Deportivo last week in Brazil and it has the advantage ahead of Thursday's match in Colombia. Cucuta will be without striker Lionard Pajoy, who got injured in his first match returning from a doping suspension.
Playing at home on Thursday, two-time champion River Plate will need to revert a 2-1 first-leg loss to Argentine rival San Lorenzo. While River lost to Boca Juniors in the local league, San Lorenzo defeated Gimnasia La Plata 2-1 to reach the top of the standings.
Sao Paulo and Nacional, each a three-time Copa Libertadores champion, will meet Wednesday in Brazil. Sao Paulo has edge over the Uruguayans, who have won only six of their 33 matches against Brazilian clubs. Two of those losses came to Sao Paulo.
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