Nicolas Sanchez scored in the 60th minute to give Argentine club Godoy Cruz a 2-1 victory over Liga de Quito on Thursday in the first group match for both in the Copa Libertadores.
It was also Godoy Cruz's first match in the history of the Copa Libertadores.
In other matches, Brazil's Gremio defeated Oriente Petrolero of Bolivia 3-0 and Atletico Junior of Colombia was a 2-1 winner over Peru club Leon de Huanuco.
Paraguay's Cerro Porteno overwhelmed Chile's Colo Colo 5-2 in the night's other match.
In the Group 8 match, Carlos Sanchez gave Godoy Cruz a 1-0 lead in the 16th, but Liga equalized in the 53rd on a header by Neicer Reasco. That set the stage for Nicolas Sanchez's winner on a header.
Liga finished with 10 men after Fernando Hidalgo was sent off in the second half.
The major upset comes just four days after Godoy Cruz humbled famous Argentine club Boca Juniors 4-1 in the opening game for both in the Argentine Clausura season.
In Group 2, Brazilian club Gremio polished off Oriente Petrolero with two goals by Douglas and one by Gilson.
Douglas scored in the 43rd on a penalty, beating Bolivian keeper Hugo Suarez. Gilson made it 2-0 in the 48th and Douglas scored his second in the 70th, scoring from a centering pass from Lucio.
Also in Group 2, Jhon Viafara gave Atletico Junior a 1-0 lead in the 23rd and Carlos Bacca made it 2-0 in the 66th. Carlos Elias scored for Leon in the 86th. The match marked Leon's first-ever match in the competition, Latin America's top club tournament.
Atletico Junior finished with 10 men when Jose Amaya was sent off in the 79th after his second yellow card.
In Group 5, Paraguay's Cerro Porteno had two goals from Argentine forward Juan Manuel Itrube. Roberto Nanni also scored twice for Cerro Porteno and Julio dos Santos added the other.
Cristobal Jorquera and Esteban Paredes scored for the Chileans.