Under the ownership of American businessman John Textor, Botafogo scored all five goals during the second half of their semifinal's first leg.
Venezuelan player Jefferson Savarino initiated the scoring in the 51st minute, skillfully placing the ball past goalkeeper Washington Aguerre. Just four minutes later, Alexander Barboza extended the lead with a close-range effort, followed by Savarino's second goal in the 55th minute.
Brazilian national team striker Luiz Henrique added the fourth goal in the 71st minute with a well-placed lob over Aguerre, and Igor Jesus, who recently represented the national team in the latest South American World Cup qualifiers, capped off the scoring in the 79th minute.
On Tuesday, Atletico Mineiro secured a 3-0 victory against Argentina's River Plate in the first leg of their semifinal. The Brazilian club previously claimed the Copa Libertadores title in 2013.
Brazilian teams have dominated the tournament for the past five years, with the last four finals being contested on home soil.
The second legs of the Copa Libertadores semifinals are scheduled for next week, with the final set to take place on November 30 at Monumental de Nunez Stadium in Buenos Aires.
Earlier, over 250 Penarol supporters were detained in Rio de Janeiro following clashes with law enforcement prior to the semifinal match. According to Rio police, the fans were involved in various acts of vandalism, looting, and destruction of property. They were prohibited from attending the match, and one firearm was recovered by the authorities.
Additionally, on Wednesday, Brazil's Cruzeiro and Argentina's Lanus played to a 1-1 draw in the first leg of the Copa Sudamericana semifinal.
On Thursday, Brazil's Corinthians will face Argentina's Racing in Sao Paulo.