The semi-final was decided on spot-kicks after Sao Paulo midfielder Ganso's 54th-minute goal levelled the tie 1-1 on aggregate at the end of 90 minutes in Brazil.
Nacional were faultless in the shoot-out as Sao Paulo struggled from the spot, with first-leg goalscorer Luis Ruiz converting the penalty to send the Colombians through to the decider.
Daniel Bocanegra made no mistake with Nacional's first penalty but the same could not be said about Sao Paulo, striker Alan Kardec skying his effort over the crossbar after slipping as he attempted to kick the ball.
Juan Valencia preserved Nacional's perfect record from the spot, despite Sao Paulo goalkeeper Rogerio Ceni getting a hand to the ball.
Ceni was the next to step up for Sao Paulo and he sent his opposing number the wrong way with the team's second attempt.
Edwin Cardona tucked the ball underneath Ceni, while Nacional keeper Franco Armani dashed Sao Paulo's hopes, paving the way for Ruiz to score the winning penalty.
Nacional will face either Boca Juniors or River Plate in next month's final.
