Goals in the last 24 minutes from Henrique and Kleber gave Cruzeiro a 4-1 aggregate victory and a place in an all-Brazilian semi-final with Gremio, who went through on Wednesday.
The night turned sour for Sao Paulo, who have won the trophy four times, when they had Eduardo sent off for a second bookable offence a minute before halftime.
Both sides are looking for their third title in South America's equivalent of the UEFA Champions League.
Argentina's Estudiantes, who won the tournament three times in a row from 1968-1970, beat Defensor Sporting of Uruguay 1-0 in La Plata to line up a semi-final against another Uruguayan side, Nacional.
Benitez, who squandered a late chance to score again, rammed home a poor clearance of Juan Salgueiro's cross following a good move down the right started by captain Juan Sebastian Veron, whose father Juan Ramon played for the title-winning side.
Estudiantes and Defensor, who upset favourites Boca Juniors in the previous round, began the tournament as outsiders and Veron said: "It's nearly 40 years since we had a semi-final.
"It's great for the club, in La Plata," he added, referring to the first leg to be played at home on June 24.
