Libertad, Arsenal progress to group stage
Jorge Burruchaga's Libertad came back from a 2-1 first-leg defeat and took the lead in the first minute when Jose Nunez fed Pablo Velazquez, who fired home.
El Nacional equalised quickly in the 12th minute, when Paul Minda netted a left-footed strike and beat Libertad keeper Rodrigo Munoz.
Nunez put the Paraguayan team ahead again in the 29th minute and Rodolfo Gamarra added another five minutes later.
With three minutes remaining, El Nacional defender Jose Enrique Madrid fouled Miguel Samudio and was shown red before Luciano Civelli made it 4-1 after a counter-attack in the fourth minute of stoppage time.
Libertad made it into Group 5 and will play against Alianza Lima of Peru, Uruguayan giants Nacional and Brazil's Vasco da Gama.
Burruchaga told reporters in Asuncion: "We were the team who always tried to attack. We were ordered and made the first step with authority. We relaxed in the second half, but had no problems.
In Peru, Argentinian side Arsenal progressed to the group stage despite a 1-1 draw with hosts Sport Huancayo.
The 3-0 win in the first leg in their homeland helped Gustavo Alfaro's Arsenal qualify to the next stage and they will play Boca Juniors, Venezuela's Zamora and Fluminense of Brazil.
Sergio Ibarra put Sport Huancayo ahead seconds before half-time and his team chased the two more goals needed to take the match to penalties, but Luciano Leguizamon came off the bench to level on the night with four minutes remaining, heading home after a Cristian Campestrini goal-kick.
Arsenal keeper Campestrini told Fox Sports: "We gained the point we were looking for. We were looking forward to the qualification. We made big effort against a team who play good football."