At F1's first foray into America for five years,
the championship leader
was 0.7 seconds faster than team-mate Mark Webber and Ferrari's Fernando Alonso.
Vettel topped the times despite missing half the session with a water leak.
McLaren drivers Lewis Hamilton and Jenson Button were fourth and fifth ahead of Ferrari's Felipe Massa.
US GP Second practice top 10
1. Sebastian Vettel - Red Bull 1:37.718
2. Mark Webber - Red Bull +0.757
3. Fernando Alonso - Ferrari +0.765
4. Lewis Hamilton - McLaren +1.030
5. Jenson Button - McLaren +1.068
6. Felipe Massa - Ferrari +1.311
7. Nico Rosberg - Mercedes +1.730
8. Bruno Senna - Williams +1.813
9. Kamui Kobayashi - Sauber +1.935
10. Michael Schumacher - Mercedes +2.397
Mercedes driver Nico Rosberg was seventh ahead of Williams's Bruno Senna, benefiting from being able to drive in first practice at this new track rather than having to give his car to reserve driver Valtteri Bottas.
For much of the first session at the new Circuit of the Americas, Hamilton and Alonso traded fastest times as Vettel worked away at learning the track and setting up his car.
But the German came alive in the closing minutes of the session, first beating Hamilton's time by 0.792 seconds and then lowering his mark again to one minute 38.125 seconds - a massive 1.418secs faster than Hamilton.
Vettel said: "This afternoon we had a little bit of a problem, we couldn't run as much as we would like to but we got two good runs, one with less fuel and one with more fuel which was important to be prepared for tomorrow and Sunday.
"Friday you need to be careful (of the lap times). The fact that it was very slippery can make a bigger difference than you think. There were one or two surprises in terms of pace. It is important we are amongst the guys at the top and we try to improve the car for tomorrow to make sure we stay there."
Hamilton said it had been a "good day", adding: "I don't know where (Vettel) got that time from but that's very quick. I don't know whether we can have that pace but we can definitely improve our car, there are some bits we can improve on."
Red Bull duo praise Austin circuit
Vettel's performance suggests he is in a strong position to further consolidate his lead in the world championship, which the 25-year-old German can win this weekend if results go his way.
German Vettel is 10 points ahead of Alonso heading into the penultimate race of the season, with the finale in Brazil next weekend.
It was an incident-packed session, where several drivers held up others, cars running off the track, plus a couple of spins at Turn One for Vitaly Petrov and Romain Grosjean and one at Turn 13 for Hamilton.
In the race-simulation runs on heavy fuel loads at the end of the session, Hamilton set the fastest time by 0.2secs from Vettel, with Alonso just 0.1secs behind the Red Bull.
Several teams were trying out new parts, including Ferrari as they desperately try to close the performance gap to Red Bull to keep Alonso's dwindling title hopes alive.
The Spaniard played around with front wings, under-nose turning vanes and a new diffuser.
United States Grand Prix 2012, day two
Saturday, 17 November: Third practice 15:00 GMT; audio and live text online. Qualifying 17:55 GMT; 5 live sports extra and live text commentary online. Qualifying highlights; 21:00 GMT, BBC Two
United States Grand Prix 2012, day three
Sunday, 18 November: Race 18:55 GMT; 5 live and live text commentary online. Race highlights; 22:25 GMT BBC One
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