The match started two hours behind schedule and Nadal, wearing a white knee brace, was greeted with thunderous applause when he appeared on the court in the 9,300-seat Ibirapuera gymnasium.
The winning duo was to play in the second round Wednesday.
As the top seed, the 11-time Grand Slam champion enjoyed a first-round singles bye and will open his singles campaign Thursday.
He lost the singles and doubles finals on Sunday at his comeback event in Vina del Mar, Chile following a seven-month knee injury absence.
"I am a bit tired after a hard week in Chile. But it was positive," Nadal said earlier in the day. "The process of recovery follows its course. As always I come here to do the best possible and hope that things turn out all right."
Sao Paulo is the second stop on Nadal's comeback to the ATP World Tour. The Spaniard won the Brazil Open in 2005 when it was held in Costa do Sauipe.