Corinthians remained the only team with a 100 percent record after three matches by beating Fluminense 1-0 at home, while Botafogo had two players sent off for fighting each other at the end of their 3-0 win over bottom team Goias.
Inter, who eliminated holders Estudiantes from the Libertadores Cup quarter-finals during the week, were the better team early on but were unable to score thanks to brilliant goalkeeper from Sao Paulo captain Rogerio Ceni.
The away side then profited from a mistake by Inter's Argentine keeper "Pato" Abbondanzieri to take the lead in the 38th minute, Brazil midfielder Hernanes scoring with a low, long-range shot.
Fernandao, who helped Inter win the Libertadores and world club titles in 2006, increased Sao Paulo's lead after the break with his first goal in his third game for the club following a one-two between Hernanes and striker Dagoberto on the left.
The teams will also meet in the Libertadores Cup semi-final in July. The Brazilian championship takes a break during the World Cup finals in South Africa (June 11-July 11).
Corinthians made it three wins in a row with a free-kick by defender Chicao in the 12th minute.
Four teams share second place two points behind Corinthians including Botafogo, who beat Goias on Saturday in a match that featured four red cards.
Botafogo strikers Caio and German Herrera, who scored the third goal, were sent off seven minutes from time with the score at 3-0 after pushing each other. The pair left the field to jeers from fans and were fined by their club.
Goias had keeper Fabio sent off before halftime for dissent and midfielder Wellington Saci was red carded in stoppage time.
Striker Vagner Love converted two penalties as champions Flamengo ended a run of two draws with a 3-1 win over Gremio Prudente at the Maracana.
