The German started the race second on the grid, but he passed leader Valtteri Bottas of Mercedes at the very first corner and never really looked back from there, as he maintained at least a two-second advantage over Bottas, who eventually finished second, throughout the closing stages of the race.
The victory at Interlagos was Vettel's 47th of his career and he admitted after the race that his quick start was pivotal to his latest success.
"It was initially a great start," the 30-year-old said. "I had a very good getaway but then I had some wheelspin. I think I surprised Valtteri a bit so that was very crucial."
Vettel has now all but guaranteed second place in the Drivers' Championship standings ahead of the final race of the year in Abu Dhabi at the end of the month, but he was quick to point out that it was a good day all round for the Scuderia, as his team-mate Kimi Raikkonen finished third in the race.
He added: "Really happy, especially for all the guys in the team back in Maranello. It's been very tough but it's great to have both cars up here."
Mercedes’ Lewis Hamilton, fresh from sealing world championship glory in Mexico last time out, claimed fourth despite starting from the pitlane, while Red Bull duo Max Verstappen and Daniel Ricciardo had to settle for fifth and sixth place respectively.
One of the stories of the day saw Williams' Felipe Massa finish seventh on what was his final Grand Prix appearance on home soil and he admitted after the race that it had been an emotional day.
"I am really emotional today because of all you guys," the Brazilian said. "Thank you very much for all the support and energy I felt here today, for making the best race I could."