Vettel lapped the Sakhir Circuit in a best time of one minute 31.683 seconds, 0.040 faster than team mate Kimi Raikkonen on the supersoft tyres.
It was the first time this season that any driver from outside the Mercedes pairing of Nico Rosberg and triple world champion Lewis Hamilton had ended practise on top.
Hamilton was quickest in all three sessions in Australia two weeks ago while championship frontrunner Rosberg led his team mate in Bahrain practices one and two on Friday.
Rosberg was third fastest in practise three, his time of 1:32.104 slower than Friday when he did 1:31.001, with Hamilton fourth.
Ferrari went well in Bahrain last year, with Raikkonen finishing runner-up, and the talk ahead of Sunday's race was that the gap with Mercedes was likely to narrow in the floodlit race if not qualifying.
The Italian team might still have a struggle to claim their first pole since Vettel in Singapore last September but practise at least threw up the chance of seeing a red car back on the front row.
Mercedes began doing practise starts towards the end of the session, however, indicating that their focus was already elsewhere. Rosberg has won the last four races and Hamilton the three before that.
The Briton has also won the last two Bahrain Grands Prix.
Finland's Valtteri Bottas was fifth fastest for Williams, who flew in a new nose overnight from the factory in Britain, and Romain Grosjean continued to surprise with the new U.S.-owned Haas team in sixth.
The Frenchman finished sixth in Melbourne on the team's debut.
Belgian rookie Stoffel Vandoorne, replacing the injured Spaniard Fernando Alonso at McLaren, lapped 14th fastest and just 0.070 slower than 2009 world champion team mate Jenson Button in 13th.
(Editing by Ed Osmond)
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