Lewis Hamilton ended up second for McLaren, over a second down on Vettel, with Fernando Alonso, Jenson Button and Mark Webber rounding out the top five.
Positions and times are likely to prove irrelevant however as the very green circuit continues to rubber-in - and teams and drivers continue to acclimatise - as the weekend progresses.
The honour of christening the circuit fell to Abu Dhabi Grand Prix winner Kimi Raikkonen, who led a host of drivers out on early, and very tentative, exploratory laps.
Sauber's Kamui Kobayashi meanwhile completed the first flying lap, a very modest 1m54.846s.
That benchmark fell rapidly: next time around he was already more than six seconds faster, while within a quarter of an hour Webber had moved it on by a full 11 seconds, dropping down to a 1m43.672s.
Still though the track was treacherous, with a litany of small offs and rear wheel drifts punctuating the action.
The trend continued even when championship rivals Sebastian Vettel and Fernando Alonso and the two McLarens of Lewis Hamilton and Jenson Button entered the fray in earnest around the one hour mark.
Of the quartet it was Alonso who was up to speed fastest, the Ferrari man lowering the benchmark to a 1m42.538s.
Hamilton was quickly up to speed however, becoming the first man to drop into the 1m40s at the session's halfway mark.
At the same time Nico Hulkenberg enjoyed the dubious honour of becoming the first man to spin at Austin, losing the rear of his Force India as he crested the blind Turn 1 apex. Sergio Perez also had a wild moment as his rear broke traction coming into the pits, although he was able to save the slide.
Alonso and Hamilton swapped top spot again as the session wore on, with the Briton pushing hard enough to run wide at T19. He was not alone however: Vettel, Felipe Massa and a litany of other drivers fell foul of the quick left-hander across the session.
Heading into the final 15 minutes Hamilton suddenly surged clear, a blistering 1m39.687s - from which he then shaved a further 0.1s – moving him over half a second clear of the field.
It appeared that would be enough to keep him top, but with three minutes to go championship leader Vettel celebrated the opening of his 100th grand prix by seizing control.
The German had already proved mighty in the first sector, but was able to improve massively in the second and third splits as he blitzed the field with a 1m38.125s set as the flag fell.
No-one else had either the time to muster an answer, leaving Vettel comfortably clear of the chasing pack.
Felipe Massa claimed sixth as the flag fell, ahead of Nico Hulkenberg, Kamui Kobayashi and Nico Rosberg, running a non-coanda effect exhaust layout for comparative purposes.
Perez rounded out the top 10 ahead of the second Force India of Paul di Resta, Toro Rosso pair Daniel Ricciardo and Jean-Eric Vergne and Raikkonen, who had to be wheeled down the pitlane as the session finished.
Pastor Maldonado finished as the fastest Williams in 16th, while Marussia's Charles Pic claimed the 'best of the rest' tag in 18th ahead of Caterham's Heikki Kovalainen.