The other two matches produced away wins, with Uruguayans Nacional beating their Paraguayan namesakes 3-0 in Asuncion and Brazil's Sport Recife winning 2-1 at Chilean champions Colo Colo.
Sao Paulo, Brazilian champions for the last year three years in a row, dominated their Group Four game but were repeatedly foiled by Medellin keeper Aldo Bobadilla, who was in inspired form.
After surviving a barrage of attacks, the Colombians took a shock lead in the 79th minute against the run of play.
John Restrepo's crossfield pass found Jackson Martinez and he pulled the ball back for Luis Arias to score with a deflected shot.
Sao Paulo, champions in 2005 and beaten finalists the following year, snatched an equaliser when Dagoberto sent over a low cross from the right and Borges somehow managed to connect with a bicycle kick to hook the ball in.
Nineteen-year-old striker Ciro played a key part as Sao Paulo's compatriots Sport Recife won their Group One game in Santiago.
Ciro was quickest to react when Paulo Baier pulled the ball back in the sixth minute to put the visitors ahead.
On the stroke of halftime, Ciro pounced on a careless Colo Colo pass and fed Wilson who added the second.
Argentine Lucas Barrios pulled one back in the 70th minute.
Uruguay's Nacional, who beat Deportivo San Martin at home last week, made it six points from two games in Group Three after beating Paraguay's Nacional 3-0.
Alvaro Fernandez and Nicolas Lodeiro gave the visitors a 2-0 halftime lead and Marcos Mondaini completed the scoring in the 63rd minute.
The Paraguayans have no points from two games.
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