Vettel spent a large part of the session in the garage as Red Bull noticed a water leak in his RB8.
Vettel was seven tenths clear of team mate Mark Webber, with Fernando Alonso in third place.
The McLarens of Lewis Hamilton and Jenson Button were fourth and fifth, ahead of Felipe Massa.
Nico Rosberg, Bruno Senna, Kamui Kobayashi and Michael Schumacher rounded out the top ten.
Abu Dhabi winner Kimi Raikkonen was only eleventh, two places ahead of team mate Romain Grosjean.
It was a disappointing day for Force India, with Nico Hulkenberg and Paul di Resta only seventeenth and eighteenth respectively.
Turn 19 once again claimed several drivers, with Alonso and Pastor Maldonado among the drivers running wide.
Maldonado also came to grief at the end of the session when he crawled to a halt in the pits with a puff of smoke coming from his engine.
Jean Eric Vergne tried to pass Heikki Kovalainen at Turn 19, but the two touched, giving Kovalainen a left rear puncture and the Finn had to slowly return to the pits having just missed the pit entry.