After a year away at Imola in 1980, the Italian GP was back at its spiritual home in Monza with Nelson Piquet and Carlos Reutemann arriving on equal points in the World Championship. The summer had been seen the emergence as a major force of Alain Prost in the Renault and he too was becoming the threat to the World Championship leaders. The switching around of tyres continued with Tyrrell deciding to go back to Goodyear at least for Eddie Cheever's car.

The field was the same as usual with René Arnoux on pole in the Renault ahead of Reutemann's Williams and Prost. Jacques Laffite was fourth in his Talbot Ligier and he was clear of Alan Jones (Williams) and Piquet while the top 10 was completed by John Watson (McLaren), Didier Pironi and Gilles Villeneuve in the fast but evil-handling Ferraris and Bruno Giacomelli's Alfa Romeo. The event was significant in that it marked the first start for the Toleman team, Brian Henton having finally qualified one of the Toleman-Hart cars in 23rd position on the grid after a season of disappointment.

At the start Pironi made an exceptional start and he was fourth at the first chicane behind Prost, Reutemann and Arnoux. By the time the field arrived on the back straight Pironi was second. It did not last long Arnoux moved to second on the fifth lap and on lap six Laffite went to third (having overtaken Jones, Piquet and Reutemann). Villeneuve followed him but disappeared with turbo failure soon afterwards. Then Laffite began to drop back with a slow puncture and it began to rain! Jacques went off.

This left the two Renaults and the two Williams cars ahead but with a gap between them. Arnoux then went off at the Parabolica, swerving to avoid Eddie Cheever's abandoned Tyrrell and so Prost was left on his own.

There was then a huge accident at the Lesmo when Watson lost control of his MP4/1. It spun into the barriers and the engine was ripped from the tub. Watson emerged unhurt but the engine went across the road, causing Michele Alboreto to crash his Tyrrell. The next to arrive was Reutemann and he had to take to the grass and so he dropped behind Giacomelli. The Alfa driver was not in luck however and on lap 26 his Alfa went into the pits with his gearbox jammed. This put Piquet into third place behind Prost and Jones and it looked like staying that way until the last lap when his engine blew, which allowed Reutemann, de Angelis and Pironi to pass him. He picked up just one point and Reutemann moved three points ahead in the World Championship.