Flu will have joint leaders Corinthians and Vasco da Gama looking nervously over their shoulders after both lost at the weekend.
Inspired by former Chelsea and Portugal midfielder Deco, who laid on both goals, Fluminense climbed to third with 56 points, two behind the leaders with five matches remaining.
Botafogo and Flamengo are a further point back in the tightest championship race since the present league format was introduced in 2003.
Fluminense, who have had the best results in the second half of the 38-match championship, inflicted a rare defeat on Inter in their Beira Rio stadium in the southern city of Porto Alegre.
Deco crossed for Rafael Moura to head the visitors into the lead in the 17th minute and teed up former Inter and Brazil striker Rafael Sobis to score the winner in the last move of the first half after Oscar's equaliser.
Other results went Fluminense's way, especially the shock 2-1 defeat for Corinthians by the virtually relegated bottom team America Mineiro.
Although they were the visitors, Corinthians had some 40,000 fans at the Parque do Sabia stadium in Uberlandia for a match the visitors were expected to win.
America, with only four wins in their 32 previous matches, had other ideas and Amaral scored with a free-kick in the 88th minute to secure the victory.
Fabio Junior had put America ahead with a 35th-minute penalty and Corinthians equalised before half-time, also with a penalty converted by defender Chicao.
Corinthians clung to their slender lead in the standings on goal difference thanks to Vasco's 2-0 defeat away to South American champions Santos.
Teenage Brazil striker Neymar sparkled again for Santos, putting them ahead with a free-kick in the fourth minute and creating a string of chances squandered by team-mates.
Finally fellow striker Borges, the championship's top scorer with 23 goals, put one of Neymar's chances away in a match marking playmaker Paulo Henrique Ganso's return from an injury he suffered playing for Brazil in a friendly against Ghana in London in September.
Ronaldinho's Flamengo crushed Cruzeiro 5-1 with a Thiago Neves hat-trick and two goals by Deivid pushing the twice South American champions closer to the relegation trap door.
