The German hit the front 25 minutes into the session and was never then displaced, despite being one of the last to switch onto soft rubber.
Having struggled for one-lap pace, McLaren did at least have the comfort of getting closer than it was able to in second practice, when Vettel enjoyed a commanding gap of more than six tenths of a second over the field.
Jenson Button got to within 0.192s of the German at the top of the timesheets, while Lewis Hamilton was fractions down the road in fourth.
The two silver arrows were split by the second Red Bull of Mark Webber, who captured third late on on his soft tyre run.
Kimi Raikkonen sealed fifth in the final minutes, while the impressive Bruno Senna - who had run third before the field switched to softs – ended sixth fastest.
In contrast to McLaren, Ferrari struggled more, although it also stuck to its own individual programme, waiting until the session's halfway mark to post its first times and then playing with drafting shortly afterward.
Fernando Alonso, looking to respond to Vettel's run of three straight wins, could only finish seventh fastest, six tenths down on Vettel.
Force India's Nico Hulkenberg, Mercedes' Michael Schumacher and the second Lotus of Romain Grosjean rounded out the top 10.
The session has begun slowly, with the first laptimes only being set a quarter of the way into the hour.
Raikkonen was the first to post a time, immediately going fastest with a 1m27.686s that kept him top until Webber and then Vettel went out.
Nico Rosberg was also out early, but quickly hit problems as he ran through the gravel while shadowing the second Lotus of Grosjean.
Even as he did, Grosjean was on his radio complaining of a lack of balance and grip, a problem echoed down the pitlane.
Sergio Perez was also struggling with a nervous Sauber and could only manage 13th fastest at the flag, five places up the road from team-mate Kamui Kobayashi.
That put him behind Felipe Massa and Pastor Maldonado in the second Ferrari and Williams respectively.
Paul di Resta was seventh before the field switched to soft rubber, but found himself dropping down the order and eventually wound up 14th, just ahead of Nico Rosberg and the two Toro Rossos.
Daniel Ricciardo had the edge in the STR intra-team battle, ending the session three tenths faster than Jean-Eric Vergne.
Heikki Kovailainen and Caterham were meanwhile best of the rest.
Rosberg's trip across the gravel and Webber's spin at the final turn were the only moments in a relatively-incident free session.