The 61-year-old Hollywood star received the award for his “extraordinary journey as a performer” before presenting his new directorial film to audiences, the Italian festival said.
Titled Modi, Three Days on the Wing of Madness, it is described as “a 72-hour whirlwind in the life of bohemian artist Amedeo Modigliani, known as Modi”.
The Rome Film Festival shared photos on its Instagram of Depp holding the golden statue, which was presented to him by Modi lead actor Riccardo Scamarcio.
For the event, the American actor donned a navy blue suit over a lemon shirt, which he teamed with a patterned tie that he left loose around his neck.
The film festival also released photos of the Oscar nominee meeting fans on the red carpet and posing for photos before the screening.
Depp has starred in numerous films over the years, but gained worldwide fame for his role as Captain Jack Sparrow in the Pirates of the Caribbean franchise.
He has often collaborated with director Tim Burton over the years, including roles in Edward Scissorhands, Charlie and the Chocolate Factory, Corpse Bride, Sweeney Todd: The Demon Barber of Fleet Street and Alice in Wonderland.
The actor has been steadily returning to the spotlight in recent years following the conclusion of a high-profile defamation case against his ex-wife Amber Heard.