The newly-crowned quadruple world champion, sporting a new helmet with the Roman numerals IV on top, lapped the Yas Marina circuit with a best time of one minute 41.349 seconds set late in the afternoon heat.
Despite track temperatures hovering around 44 degrees, and air temperature of 36, Vettel lapped 0.222 quicker than Australian team mate Mark Webber. The pair were also one-two in Friday's second practice.
The 26-year-old German, who clinched his fourth successive title in India last weekend, will be chasing his seventh win in a row on Sunday in the day-to-night race under the banks of floodlights.
Behind the pair was Frenchman Romain Grosjean, yet to win a race but considered possibly Vettel's biggest rival after finishing third in his last three grands prix.
Ferrari continued to find the hard and soft tyres not to their liking with Fernando Alonso 11th and Brazilian Felipe Massa 14th.
Marussia's Jules Bianchi spun and hit the barriers at turn one in the only incident of the session.