Prost signed to join Ferrari in 1990, replaced Gerhard Berger and partnered with Britain's Nigel Mansell (Berger took Prost's seat at McLaren). Prost won five races for Ferrari that year, in Brazil, Mexico, France, Britain and Spain. Notable among these was the Mexican Grand Prix, where he won after starting in 13th position. In both the Mexican and Spanish races, he led Mansell to Ferrari 1–2 finishes.

The championship once again came to the penultimate round of the season in Japan with Prost trailing his McLaren adversary, Ayrton Senna, by nine points. As in 1989, a controversial collision between the two settled the race. Prost finished the season seven points behind Senna, and his Ferrari team were runners-up to McLaren.