World champion Vettel started on pole at Interlagos and, while he was briefly overtaken by Nico Rosberg early on, the German recovered to lead for the remainder of the race.
The victory ensures that Vettel equals double world champion Alberto Ascari's record of nine consecutive race victories, with team-mate Webber claiming a Red Bull one-two in his final Grand Prix before retiring from the sport.
Ferrari's Fernando Alonso took the final spot on the the podium, although it was Mercedes who took second place in the constructors' championship.
Jenson Button's fourth-place finish ensured that McLaren finished the season without a podium for the first time since 1980, with Rosberg a place further back.
Rosberg had overtaken Vettel on the first lap after racing away from the lights, although he was not in the lead for long as the champion returned to the front in the first turn of the second lap.
Meanwhile, Lotus' Romain Grosjean pulled out on the fourth lap after an engine problem caused smoke to billow out of his car, while Lewis Hamilton lost third place as he was overtaken by Alonso and Webber.
Vettel soon extended his lead to five seconds, as he looked to round off the calendar in style, with Webber edging inside Alonso to take second, while Hamilton recovered to move ahead of Rosberg, who had dropped to sixth by the 14th lap.
At the front, Vettel's dominance continued, as he extended his advantage to over 10 seconds ahead of Webber.
Felipe Massa, featuring in his final race for Ferrari in front of a home crowd, was running fourth when he was penalised for crossing the pit line in lap 33. His drive-through penalty cost him as he ended the race in seventh.
Vettel and Webber both opted to pit on lap 48, with the German remaining in the lead despite a slow stop as Alonso, who stuck with the softer tyres, kept the Australian firmly in his sights.
Hamilton, meanwhile, dropped out of the points when he collided with Valtteri Bottas in the Williams. The Brit managed to remain on the track but he was handed a drive-through penalty for the incident, ending the race in ninth as a result.
As the rain threatened to cause problems, just as it had in qualification, Vettel's lead had been trimmed to 8.5secs with five laps remaining.
However, the German had already done enough as he rounded off another record-breaking season in familiar style.