Ferrari's Fernando Alonso, 10 points behind the championship leader with one round to come after Sunday, set only the ninth quickest time in qualifying at Austin's new Circuit of the Americas.
"It was a bit closer than I wanted, but fantastic to start on the front and on the clean side," said Vettel, 25, of his sixth pole of the season and 36th of his career, after beating McLaren's Lewis Hamilton to the top slot.
Alonso, the only driver who can deny Vettel the title, gained one position immediately with France's Romain Grosjean handed a five-place penalty for an unscheduled gearbox change.
That moved the determined Spaniard up to eighth on the starting grid and right behind Brazilian team mate Felipe Massa in sixth.
"I think the car is more or less the same as the last race, we were position seven in Abu Dhabi and here we are position eight," Alonso, who finished second in that race at Yas Marina, said.
"So more or less it is the same and we will try to recover good places on Sunday that normally is our strong point so I still believe that tomorrow we can score more points than Sebastian.
"The race is long, anything can happen and we need to keep confident and optimistic because normally the race pace improves a lot," added the Ferrari driver, who must finish at least fourth if Vettel wins in order to stay mathematically in contention for the finale in Brazil.
Alonso will have no problems getting ahead of Massa but reeling in Vettel, the dominant driver of the closing stages of the season, will be another matter.
With Formula One back in the United States for the first time in five years, Vettel has looked right at home in Texas with the fastest times in all three practice sessions at the sport's newest venue.
While Vettel will have one eye on Alonso, he is likely to have the other on Hamilton alongside.
The Briton, last winner of a US Grand Prix at Indianapolis in 2007, was just a 10th of a second slower and has been quick around the undulating circuit all week.
"We are very happy with the result but so far nobody has scored any points. We've seen how things quickly can change from the last race," said Vettel, who started from the pit lane in Abu Dhabi due to a fuel irregularity discovered after qualifying third.
Hamilton retired while leading that race from pole.
Red Bull are set to clinch the constructors' title for the third year in a row on Sunday and have Australian Mark Webber in third place on the grid with Finland's Kimi Raikkonen fourth for Lotus.
"We are not really trying to pay too much attention to the championship," said Red Bull team boss Christian Horner. "Our focus is very much on this race and now we have completed qualifying it turns to the race tomorrow afternoon.
"We are trying to treat this race exactly as we have treated the previous 18 races and we'll apply the same focus to tomorrow."
Seven times world champion Michael Schumacher, who is retiring at the end of season, will hope to wave goodbye to his American fans with a good result after qualifying fifth for Mercedes.
"Qualifying was better than we expected, especially as we have struggled over the weekend and have worked hard to make progress," said Schumacher, who has four US Grand Prix wins on his resume.
"It will make a big difference here whether you start from the clean or dirty side of the grid, so gaining an extra place due to Grosjean's penalty was a nice surprise.
"The car looks reasonably consistent for the race and I would like to achieve the maximum result possible tomorrow."
Germany's Nico Hulkenberg, in a Force India, will be alongside Alonso on the fourth row with Grosjean and Venezuelan Pastor Maldonado, for Williams, behind.
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