After spending a lap behind Rosberg, Vettel never lost the lead, even with an unescheduled and confusing pit stop.
There was still a couple of battles, however. Mercedes and Ferarri were squabbling over second in the constructor's championship but were struggling for outright pace.
Mercedes grabbed second despite Alonso's first podium since Singapore.
PRACTICE AND QUALIFYING
Vettel was never headed during any session, all of which were conducted in wet conditions.
Qualifying was swinging between damp and wet, catching out McLaren's Perez who crashed into a wall, tearing wheels from the car but leaving him uninjured.
Vettel triumphed while the top five was settled in the dying moments of qualifying, with Rosberg joining him on the front row. Alonso came in a strong third, Webber fourth and Hamilton fifth.
Perez's crash relegated him to 19th after a gearbox change forced by his accident. Daniel Ricciardo lined up seventh.
As it had been all weekend, race day was dark and the conditions changeable. The cars went to the grid on slicks, hoping the race might stay dry.
Vettel got a good start but Nico Rosberg got a great one. Alonso tried one of his huge leaps but Hamilton had his measure, cruising past as the Spaniard was bottled up behind Vettel. Massa made up three spots in his final Brazilian Grand Prix for Ferrari, almost getting by Webber.
Perez pushed di Resta wide at turn 12, a favour the stewards investigated but left alone.
Vettel went past Rosberg on the main straight at the end of the lap and Webber took Hamilton around the outside in a heart-in-mouth moment at turn six. Alonso wasn't messing about either, passing Hamilton and taking off after Rosberg, duly passing him.
Romain Grosjean, who was on his way forward had massive engine failure, his Renault V8 giving up on lap four. It left a massive plume of smoke, the power unit seemingly protesting its exit from the sport in one last spectacular show.
Webber got in behind Rosberg as the DRS became available. The Red Bulls took a pre-race gamble to go with less wing to take advantage of the Interlagos main straight to get by their competition. He went around the outside of Rosberg at the Senna esses.
Jenson Button was having some fun, reaching eighth place with a number of good passes. He'd had a dismal qualifying but he was making up for it with good race pace.
By lap 10, Webber was within a second of Alonso and stalking him for third. Rosberg radioed his team to complain of a lack of grip, his team telling him to give Lewis an easy time.
Vettel was miles ahead, with a seven second lead. Webber began a sustained attack on Alonso on lap eleven while Hamilton got by Rosberg without fuss. Massa passed the struggling German on lap 15, who was constrantly on the radio, begging for new tyres.
Webber got through at the end of lap 12, cruising by the Ferrari on the straight and holding the place before driving away.
Perez, in his last race for McLaren, enjoyed a good battle with Williams' Valtteri Bottas while Button marched his way through the upper reaches of the top ten, taking seventh from Hulkenberg.
Webber set off after Vettel, but the German stretched his lead, eager to take his ninth consecutive win.
Kovalainen was having a good race, pitting and then promptly passing both Bottas and Vergne in gutsy moves.
Massa pitted at the end of lap 19, replacing his medium tyres with another set, Alonso following him in two laps later, pitting from fourth. Hamilton, too, came in for new tyres.
Button continued his excellent race, firing around the outside of Sauber's Esteban Gutierrez.
Rosberg was finally able to pit at the end of lap 22, dropping him behind Button.
Webber pitted from second on lap 24 and had a long-ish stop of five seconds with a left-rear wheel problem. He fell behind Fernando Alonso. Vettel came in next lap, and had a 2.6 second stop.
Webber again mounted a sustained attack on Alonso to eventually prevail on lap 26. Alonso didn't go without a fight, however, with the Ferrari car staying on the Red Bull for the next lap.
On lap 30, Massa was battling Mercedes' Lewis Hamilton. The Briton raidioed in with a KERS problem, the Ferrari team immediately informing their man in fourth. The Brazilian had to hold his breath, however, as he was investigated for crossing the pit entry line a little too enthusiastically.
He was awarded a drive-through penalty, following reprimands for drivers who did it during practice and a warning from race control. He wasn't pleased, filling the airwaves with invective while he stayed out as long as he could before serving the penalty.
Hamilton wanted to pass, but he was repeatedly told by his team to stay away from the Ferrari. Massa took the penalty and spent his time in pitlane gesticulating and shaking his head. He dropped back to eighth.
On lap 42, the mist began to move in on the Interlagos circuit, with rain threatening, but in the distance.
Massa and Button stopped on lap 45 while Perez and Rosberg stopped at the end of that lap. Rosberg stayed ahead of Perez.
Massa and di Resta were battling for ninth and tenth, the Brazilian fighting hard to regain lost ground. di Resta, in his last race for Force India, defended hard but was unable to keep the DRS-assisted Ferrari behind.
On 47, Bottas got a good run on Hamilton, getting around the outside of him on the straight. Hamilton didn't appear to see the Finn, the two cars touching rear wheels. Bottas' wheel broke, sending him into the gravel while Hamilton's rear tyre came off the rim.
Hamilton copped a drive through for the collision. Like Massa, he wasn't happy about the penalty, but quickly took it.
Vettel shot into the pits, fearing a safety car, but the Red Bull team weren't ready, expecting his teammate. Webber came in behind the race leader but only lost a small amount of time as Vettel left the box. Either way, Webber halved Vettel's lead, but had Alonso in his wake.
The stewards awarded another penalty, van der Garde scoring one for ignoring blue flags.
Jean-Eric Vergne managed to spin Pastor Maldonado at turn one after an abortive attempt to pass the Williams. Maldonado got going again and for some reason felt it was incumbent upon him to block Button, who was lapping him.
Vergne escaped a penalty in the post-race investigation.
Vettel took his ninth consecutive win and the last V8 victory for Renault power. Webber came home a fine second after starting fourth, bringing to a close his Formula One career. He removed his helmet and gloves while completing his final warm down lap while Vettel performed a series of donuts, as did Felipe Massa.
"It was nice to take the helmet off for the final lap. In this sport it's not always possible to give things a personal touch. We have the helmets on all the time, so the fans don't always see a Formula One driver in a car without a helmet," Webber said.
"Seb and I have had our challenges over time and it's easier to have a relationship with Fernando, as he's in another team, but to finish on the podium with those two guys - well, they have been the best of this generation. I have raced them a lot and to finish with those guys was nice for me because it meant a lot, showing that I can drive well at the end of my career and that I got the timing right."
Jenson Button gave McLaren their best finish of the season with fourth after a brilliant drive. Rosberg and Hamilton took enough points to cement second in the constructor's championship to beat Ferrari.
Daniel Ricciardo completed his last race for Toro Rosso in tenth, again beating teammate Vergne home.
"We were not very quick from the start and I was struggling with cold graining on the front right. We did try and rebalance it during the race, but we struggled in terms of pure pace, so I was quite happy to come away with a point."
Formula One returns in March at the Australian Grand Prix, the first without Mark Webber since 2002.
- Sebastian Vettel - Red Bull-Renault - 1h32m36.300s
- Mark Webber - Red Bull-Renault +10.452s
- Fernando Alonso - Ferrari +18.913s
- Jenson Button - McLaren-Mercedes +37.360s
- Nico Rosberg - Mercedes +39.048s
- Sergio Perez - McLaren-Mercedes +44.051s
- Felipe Massa - Ferrari +49.110s
- Nico Hulkenberg - Sauber-Ferrari +1m04.252s
- Lewis Hamilton - Mercedes +1m12.903s
- Daniel Ricciardo - Toro Rosso-Ferrari +1 lap
- Paul di Resta - Force India-Mercedes +1 lap
- Esteban Gutierrez - Sauber-Ferrari +1 lap
- Adrian Sutil - Force India-Mercedes +1 lap
- Heikki Kovalainen - Lotus-Renault +1 lap
- Jean-Eric Vergne - Toro Rosso-Ferrari +1 lap
- Pastor Maldonado - Williams-Renault +1 lap
- Jules Bianchi - Marussia-Cosworth +2 laps
- Giedo van der Garde - Caterham-Renault +2 laps
- Max Chilton - Marussia-Cosworth +2 laps
Charles Pic Caterham-Renault 58 laps
Valtteri Bottas Williams-Renault 45 laps
Romain Grosjean Lotus-Renault 2 laps