The McLaren driver, in his last race for the team before moving to Mercedes, posted the quickest time of the session early on, taking advantage of the extra set of 2013-spec tyres, which all teams worked with in the opening 90 minutes of running.
Hamilton's time of 1m14.131s was only 0.009s better than that of Sebastian Vettel, second in the Red Bull, the German's time set on this year's rubber. Team-mate Mark Webber was third, also less than a tenth off a second behind Hamilton.
Jenson Button was fourth, while championship contender Fernando Alonso finished in fifth position in the Ferrari, albeit over two tenths of a second off the best time.
Felipe Massa was sixth in the second Italian car, with Romain Grosjean, Paul di Resta, Pastor Maldonado and Nico Hulkenberg completing the top ten.
Williams's Valtteri Bottas was the first man to post a time in the first minutes of the session, the Finn completing a lap of 1m21.218s that kept him on top until Sergio Perez went some four seconds quicker 12 minutes into the session.
The Mexican then went around two seconds quicker to post a 1m15.869s.
Fifteen minutes in, Hamilton jumped to the top of the times with a 1m14.374s in the McLaren, the Briton using the 2013-spec tyres available for the teams for the session.
Moments later, the former world champion improved to a 1m14.131s that put him nearly two seconds clear of the rest of the field. That would be enough for him to stay ahead of his rival until the end.
Vettel moved up to second place 27 minutes in, posting a time just three tenths off Hamilton's best, the German also using the prototype rubber from Pirelli. The world champion improved his time later in the session when running with this year's hard tyres, but he still fell short of Hamilton's time by 0.009 seconds.
With the teams not using the medium tyres at their disposal, the top times stayed mostly unchanged during the remainder of the session.
Abu Dhabi Grand Prix winner Kimi Raikkonen missed most of the running as his mechanics worked on his car, the Finn only posting a time with just ten minutes to go after being hit with apparent engine problems.
The struggling HRT team also restricted its running, with Pedro da la Rosa and Narain Karthikeyan managing just an installation lap early on and not returning to the track until there were 35 minutes left on the clock.
The 90 minutes of action were mostly incident-free except for a spin by Massa with nine minutes to go, the Brazilian losing control of his car at Turn 9.
Vettel, who has won five times this season, will be champion if:
- He finishes in the top four
- He finishes 5th, 6th or 7th but Alonso does not win
- He finishes 8th or 9th and Alonso does not finish better than third
- Alonso does not finish better than fourth
Alonso, who has already won three times this season, will be champion if:
- He wins while Vettel does not finish better than fifth
- He finishes 2nd while Vettel does not finish better than eighth
- He finishes in the top three, while Vettel does not finish better than 10th
In all cases where there would be a tie at the end of the Brazilian GP, Vettel would be crowned champion due to the number of wins this season, he leads 5-3 before the final round.