Argentina suffered a shock defeat at the hands of Venezuela in the 2014 World Cup qualifiers as Colombia and Chile enjoyed wins.
Athletic Bilbao defender Fernando Amorebieta scored the only goal of the game as Venezuela beat Argentina 1-0 at home to record a first ever victory over the two-time World Cup winners.
Venezuela, who had started the qualifiers with a 2-0 defeat by Ecuador, struck just past the hour mark when Amorebieta headed home Juan Arango's corner.
Visiting keeper Mariano Andujar had earlier kept Argentina in the game as the Albicelestes followed up an opening game win over Chile with a surprise defeat.
Chile bounced back from the loss to Argentina by posting a 4-2 triumph over Peru in Santiago following an entertaining encounter.
Waldo Ponce put the home side ahead after a minute, Jean Beausejour netted on 18 minutes and Gary Medel further increased the lead just after half-time.
Peru got back into the game through quick-fire goals from Claudio Pizarro and Jefferson Farfan, but Humberto Suazo's goal on 63 minutes settled Chile's nerves.
Colombia secured a winning start to their quest for qualification after claiming a 2-1 triumph away to Bolivia.
Dorlan Pabon put Colombia ahead two minutes after the interval, but Walter Flores equalised with a long-distance shot with only five minutes to go.
However, Atletico Madrid striker Radamel Falcao scored a last-gasp winner for Colombia to sink Bolivia, who had lost to Uruguay in their opening match.
Copa America champions Uruguay were held 1-1 away from home by Paraguay after Diego Forlan's goal was cancelled out by an injury-time equaliser from the hosts' Richard Ortiz.