Libertadores: Giuliano strike gives Inter edge
The midfielder, who came on in the 65th minute, collected Andrezinho's pass with his back to goal and scored with a shot on the turn to give his side a slender advantage over the team they beat in the 2006 final.
It was the 20-year-old's fourth goal of the competition, his tally including the dramatic last-gasp winner that eliminated defending champions Estudiantes in the quarter-final.
Three-times champions Sao Paulo were always on the back foot and only an outstanding performance from their stalwart goalkeeper Rogerio Ceni prevented them from suffering a heavier defeat.
The second leg will be played at the Morumbi next week.
Mexico's Guadalajara were held to a 1-1 draw at home by Universidad de Chile in the other tie played on Tuesday.