Flamengo thrashed Olimpia in the last round to remain on course for a second triumph in three years in this competition, while Barcelona knocked out Fluminense.
Match preview
Flamengo's impressive run of form, which had seen them win seven and draw one of their last eight matches, came to an end at the weekend as they lost 1-0 at home to Gremio.
That setback leaves the Scarlet-Black third in the Brasileiro standings, 11 points off leaders Atletico Mineiro with a couple of games in hand to play.
Finishing top of the pile in Brazil for a third year running now seems unlikely, but Flamengo do at least look good value to go all the way on the continent.
After going through the group stage unbeaten to finish top, Renato Gaucho's men then eased past Defensa y Justicia and Olimpia in the last 16 and quarter-finals respectively.
Barcelona will provide a tough test in the semis, though, having topped a group that contained Boca Juniors before eliminating Velez Sarsfield and Fluminense in the knockouts.
The reigning champions of Ecuador are the only non-Brazilian side left in the competition, with Palmeiras and Atletico Mineiro contesting the other semi-final.
Fabian Bustos's men have never previously won the Libertadores, but they did finish as runners-up in 1990 and 1998 during a successful period for the club.
However, they have hardly made the best of starts to their current domestic campaign, having lost three of their opening seven matches to find themselves down in seventh place.
As Fluminense discovered in the last round when being eliminated on away goals, however, Barcelona should not be written off ahead of the first leg at the iconic Maracana.
Flamengo Copa Libertadores form:
Flamengo form (all competitions):
Barcelona SC Copa Libertadores form:
Barcelona SC form (all competitions):
Team News
Flamengo produced their worst performance under Renato in the loss to Gremio, which may force the home boss to make some changes on Wednesday.
However, Renato has already stated that he will not take any risks on the fitness of Filipe Luis, Diego Ribas, Kenedy and Giorgian de Arrascaeta and new signing David Luiz.
Gabigol has 12 goals in 14 appearances in all competitions this term and will start up top, likely flanked by Andreas Pereira and Bruno Henrique.
As for Barcelona, they have been boosted by Mario Pineida, Bruno Pinatares and Adonis Preciado's return to fitness ahead of this showdown.
All three players are expected to start the match, with Damian Diaz and Gonzalo Mastriani the favourites to lead the attack.
Bustos recently admitted to being concerned by his side's defensive record, but Fernando Leon and Williams Riveros should get the nod at the back here.
Flamengo possible starting lineup:
Alves; Matheuzinho, Caio, Henrique, Ramon; Arao, Maia; Pereira, Ribeiro, Henrique; Gabigol
Barcelona SC possible starting lineup:
Burrai; Castillo, Leon, Riveros, Pineida; Pinatares, Molina, Martinez, Preciado; Diaz, Mastriani
We say: Flamengo 3-1 Barcelona SC
Flamengo have been pretty ruthless in the Copa Libertadores so far, scoring a combined 14 goals in their two-legged wins over Defensa y Justicia and Olimpia in the last two rounds.
Barcelona are certainly no pushovers and are left to fly the flag for the rest of the continent, but we cannot see them coming away from the Maracana with a positive result.