Nannini also made appearances in the World Sportscar Championship for Martini, winning the 1000km of Kyalami in 1984 and entering three editions of the 24 Hours of Le Mans.

He was granted an FIA Super License in 1986—having been controversially denied one the year prior—and made his Formula One debut at the Brazilian Grand Prix with Minardi.

In October 1990, Nannini severed his right forearm in a helicopter accident at his vineyard in Siena, ending his Formula One career with one win, two fastest laps and nine podiums.

Though his best season saw him only seventh overall in 1983, he was signed by Lancia to drive their fast but fragile LC2 prototype in the World Sportscar Championship, setting fastest lap at the 1984 24 Hours of Le Mans where he finished eighth with Bob Wollek, and later that year winning the 1984 1000 km of Kyalami with Riccardo Patrese.

The car was uncompetitive and unreliable (Nannini was classified only four times from 30 starts with the team), largely due to its disappointing Motori Moderni V6 engine.

The following year, in his spare time, Nannini paired with veteran road race driver Giorgio Marin to win the 1987 Mille Miglia.

With Boutsen leaving for Williams Nannini was promoted to team leader at Benetton alongside young Englishman Johnny Herbert and delivered a number of strong performances, especially at Suzuka.

Nannini was eventually passed by Senna who went on to cross the finish line first, however, the Brazilian was subsequently disqualified for missing the chicane following his collision with Prost.

On 12 October 1990, the week after the Spanish Grand Prix, where he had finished third, Nannini was involved in a helicopter crash over his Siena vineyard, suffering a severed right forearm.

He agreed to take part in the short-lived Grand Prix Masters championship for Formula One veterans, alongside drivers including his former Benetton teammate Johnny Herbert.