The film, an ode to American wanderlust and the highs and lows of the open road, has won the top honour in a competition billed as a relaunch of global cinema bruised by the coronavirus crisis.
About 6,000 people are expected to turn out this year – about half the festival's usual number – as border restrictions around the globe have limited the ability of many to travel.
The 69-year old Oscar winner, known for acclaimed films such as “Talk to Her”, “Volver” and most recently his loosely autobiographical portrait “Pain and Glory”, made his debut at the festival in 1983 with the comic drama “Dark Habits”.
The Italian festival created controversy over the inclusion of Netflix productions and the inclusion of just one female director in the competition.
Guillermo del Toro's beat contenders including George Clooney's "Suburbicon" and Alexander Payne's "Downsizing."
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