Despite eight years at the pinnacle of the sport and two world championships, Senna had never won the Brazilian Grand Prix before arriving at Interlagos in 1991. He described the pursuit of a home win as an obligation to his country. A pre-qualifying session held on the Friday morning saw JJ Lehto top the timesheets in a Dallara, ahead of Andrea de Cesaris and Bertrand Gachot for Jordan, and Emanuele Pirro in the second Scuderia Italia Dallara. Senna qualified on pole for the main event, ahead of Riccardo Patrese and Nigel Mansell, with Gerhard Berger, Jean Alesi, and Alain Prost completing the top six.
Senna made a perfect start from pole position to lead Mansell, Patrese, Alesi, Berger, and Prost. He built a lead of approximately three seconds by lap eight. Mansell closed the gap to 0.7 seconds by lap twenty. Prost pitted for fresh tyres on lap 17, positioning himself to avoid being stuck behind Nelson Piquet's Benetton. Mansell pitted on lap 26 but the stop was poor, lasting over fourteen seconds and dropping him to fifth behind Patrese, Alesi, and Berger.
After Senna and Patrese completed their own pit stops, Mansell was seven seconds behind the leading McLaren. On lap 50 Mansell was forced in for a second tyre stop after a puncture caused by track debris. He resumed the chase, and by lap 60 had set the fastest lap and was closing rapidly. What the watching spectators did not know was that Senna's gearbox had been failing progressively — fourth gear had gone, and by lap 60 only sixth remained. To maintain sixth through slow and medium corners meant the car nearly stalled on multiple occasions. Mansell's gearbox failed him first, slamming suddenly into neutral and pitching the Williams into a spin that retired him on lap 61.
With Patrese now behind him and closing at approximately four seconds per lap — his own gearbox suffering — Senna held on. Rain fell in the closing laps. Senna gestured urgently to officials to end the race early; the flag was not shown. He crossed the line 2.9 seconds ahead of Patrese. Berger, who had survived a small fire on the grid and a sticking throttle, completed the podium ahead of Prost, Piquet, and Alesi.
The sustained effort of driving a single-geared car through the final laps produced severe physical consequences. Senna suffered muscle cramps and fever. After stopping on circuit he was almost unable to move unassisted and had to be lifted from the car and driven to the podium in the medical car. Once on the podium he barely managed to raise the trophy.
Senna reflected on the race: "I noticed Patrese getting closer and actually thought I wasn't going to win. However, I thought I had an obligation to win in Brazil." He described it as "the hardest-fought one" of his career to that point. The victory began an early-season run of four consecutive wins that underpinned his 1991 championship title.