Built during May and introduced at the French Grand Prix it initially looked to have the potential to run at the front.

Alain Prost qualified on the front row and took the lead, and although he was eventually passed by Nigel Mansell in his Renault powered Williams FW14, a second place in the car's first race looked promising.

The chassis of the 643 was a total redesign over the 642 which suffered inconsistent handling issues and was designed to allow for softer suspension travel, as per Prost's request.

The V12 engine was upgraded six major times during 1991, with the final evolution used from Portugal to the end of the season.

The chassis itself had two revisions, the first after the French Grand Prix—which saw a relocation of the exhaust exits from underneath the car, and Belgium which saw minor alterations to the body cover.