Veteran midfielder Juan Sebastian Veron was back in action as Estudiantes opened their account in the Copa Libertadores, while Atletico Mineiro lost for the first time.
Veron made his return to professional football last week and the 42-year-old club president took to the field again in Estudiantes' 1-0 win at home to Atletico Nacional on Wednesday.
The former Argentina, Manchester United and Chelsea star - who made himself available after fans reached his target of box sales in Estudiantes' new stadium - played 55 minutes as Javier Toledo scored the winning goal in the first half.
Veron's free-kick was saved Franco Armani in the 38th minute but Toledo was on hand to chest home the rebound.
The win saw Estudiantes collect their first points after three games in Group 1.
Brazilian side Mineiro tasted defeat for the first time in the competition this season, going down 1-0 at Libertad in Group 6.
Angel Cardozo Lucena's 27th-minute goal settled the contest in Asuncion, Paraguay.
Diego Bielkiewicz scored a first-half brace as Deportes Iquique crushed hosts Zamora 4-1 in Group 8, while Group 2 leaders Santos were held to a goalless draw by Santa Fe.