German Vettel lapped the damp Albert Park circuit in one minute 26.067 seconds on slick tyres, more than two seconds ahead of second-fastest team mate Kimi Raikkonen.
Mercedes' champion Lewis Hamilton, who topped the timesheets in both of Friday's practice sessions in warm and dry conditions, was confined to the garage for half the session with an apparent steering wheel problem.
The Briton finally emerged to post the eighth fastest lap on intermediate tyres behind seventh placed team mate Valtteri Bottas.
Sauber's Marcus Ericsson was third quickest ahead of Red Bull's Max Verstappen, both of whom were on slicks, but the times may have little bearing on qualifying (0600 GMT).
The lakeside circuit is likely to dry out further and encourage teams to push for quick times on the slick tyres.
(Editing by Peter Rutherford)
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