Vettel, who holds a 53 point lead over Ferrari's Fernando Alonso with seven races remaining this season, clocked a best time of one minute 44.173 seconds in the 60 minute session.
Romain Grosjean showed some good pace throughout the session in his Lotus to finish second fastest, 0.191 seconds behind Vettel as the sun set on another hot, humid and dry day in the Southeast Asian citystate.
Nico Rosberg was third quickest in his Mercedes (1:44.741) but the German was more than half a second slower than Vettel, who had enjoyed a similar advantage after second practice on Friday.
Vettel's Red Bull team mate Mark Webber was fourth fastest with 2008 world champion Lewis Hamilton fifth for Mercedes as the cars set up to make the most of the high downforce layout in Singapore dominated again.
Vettel, winner of the last two races at the Marina Bay Street Circuit, had predicted on Friday a close challenge from Mercedes during qualifying, which was scheduled to begin at 1300 GMT.
Spaniard Alonso was sixth fastest for the second consecutive session, more than a second down on Vettel.
Alonso's Brazilian team mate Felipe Massa was 10th quickest while Kimi Raikkonen, who will join the Spaniard at the Italian team next season, was down in 12th for Lotus.
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