Jenson Button fastest in final Brazilian GP practice
Vettel, who is 13 points clear of sole rival Fernando Alonso, was 0.057 slower than the Briton whose team mate Lewis Hamilton dominated both of Friday's sessions at Interlagos.
Ferrari's Alonso, who must finish on the podium in what looks likely to be a rain-hit race on Sunday if he is to have a hope of securing his third title and deny Vettel a hat-trick, was eighth fastest.
Even if the Spaniard were to win the race in Brazil, his championship efforts will be in vain if Vettel finishes fourth or higher.
Button's time of one minute 13.188 was comfortably the fastest of the weekend so far and suggested McLaren could make life very difficult for the title contenders.
However much will depend on the rain holding off until after qualifying later on Saturday, with some forecasts suggesting the final session could be wet.
The frontrunners will need no reminding that in 2010, Germany's Nico Hulkenberg put his Williams on pole against all the odds in just such tricky weather conditions.
Australian Mark Webber was third fastest on Saturday with Hamilton fourth ahead of his final qualifying session for McLaren before moving to Mercedes next season.
Frenchman Romain Grosjean was fifth fastest for Lotus but his team mate Kimi Raikkonen, winner in Abu Dhabi this month, managed only three laps before pulling over with a cloud of smoke coming from his car's blown engine.
The Force Indias of Paul Di Resta and Hulkenberg lapped sixth and seventh fastest.
Brazilian Bruno Senna, whose place at Williams looks uncertain, spun and forced Michael Schumacher to take avoiding action.
Sunday's race will be seven-times champion Schumacher's last, with the 43-year-old heading into retirement after a disappointing comeback with Mercedes. The German was 15th fastest.
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