Zaniolo became the youngest AS Roma player ever to score for the Azzurri when he slotted home after just nine minutes in Palermo - supplanting Daniele De Rossi in the process.
The attacking midfielder then added another in the second half, as Roberto Mancini's side completed an unbeaten qualification campaign ahead of Euro 2020.
Zaniolo was the only Roma player to play a part in the game, as club captain Alessandro Florenzi watched events from the bench.
Gianluca Mancini and Leonardo Spinazzola had previously been withdrawn from the squad.
Elsewhere in European qualification, Mert Cetin made his debut for Turkey as a late substitute in their 2-0 win over Andorra.
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