The Red Bull driver posted the best time of the weekend with a lap of 1m36.435s near the end of the session, outpacing Mercedes rival Lewis Hamilton by 0.133 seconds and the Force India of Adrian Sutil by less than two tenths.
Vettel's team-mate Mark Webber was fourth fastest in a very evenly-matched session, the Australian just 0.178s adrift.
Yesterday's pacesetter Kimi Raikkonen had to settle for fifth position after complaining about the handling of his Lotus.
Although all drivers jumped onto the track right at the start of the session, it was the Caterhams of Charles Pic and Giedo van der Garde who set the early pace as the frontrunners took things easy.
Ten minutes in, Raikkonen moved to the top of the times as he posted a 1m38s lap, soon to be bettered by Mercedes's Nico Rosberg and minutes later by Sutil in the Force India, the German the first man to lap in the 1m37s bracket.
Rosberg returned to first post briefly before team-mate Hamilton outpaced him by over three tenths with a lap of 1m37.527s, still far from the pace set by Raikkonen on Friday.
Ferrari's Felipe Massa was the last man to complete a timed lap, the Brazilian not returning to the track until half the session was gone.
Rosberg fitted the medium tyres to move back into first position with the first lap in the 1m36s at the 32-minute mark as Webber and Vettel sat at the bottom of the times, the Red Bull duo still seemingly struggling with the durability of the tyres.
Hamilton's first run on mediums with 20 minutes to go proved to be the fastest lap of the weekend, improving on Raikkonen's best from Friday by 0.001 seconds. Webber left the bottom of the times moments later, using the medium tyres to finish 0.045 seconds behind Hamilton.
Vettel, still slowest with 16 minutes of the session left, completed his first lap on mediums to move into sixth position.
Sutil jumped up to second place with less than 10 minutes remaining, finishing just 0.020s behind Hamilton.
With just over three minutes left, Vettel set a new benchmark in the medium tyre-shod Red Bull, the world champion's 1m36.435s putting him over a tenth ahead of his closest rival.
Except for a few off-track excursions, the session was incident-free.
- Sports & Recreation
- Motor Racing
- Lewis Hamilton
- Kimi Raikkonen
- Mark Webber
- Adrian Sutil
- Force India