Winner of last year's Copa Sudamericana, Sao Paulo got off to a fast start in front of a strong 50,000 home support with Paulo Ganso converting Aloisio's assist after 21 minutes.
But it all went sour in the shadows of half-time when defender Antonio Carlos put the ball into his own net to make it 1-1 at the break.
Despite conceding the majority of possession, Ponte Preta struck again through Leonardo Goncalves Silva on 53 minutes before Uendel Pereira Goncalves scored the third away goal in the 71st minute.
The result spoiled the occasion of Sao Paulo goalkeeper Rogerio Ceni playing his 1,116th match for the club - equalling Pele's total for Santos.
Ponte Preta will host the second-leg of the tie in Mogi Mirim on November 27.
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