The bus was on its way to Niagara Falls from New York when the collision happened in Pennsylvania's Pocono Mountain region, according to US media reports.
The driver – 54-year-old Alfredo Telecamaco, from New York – was among those killed.
A 70-year-old from Brescia and a pharmacist from Vicenza, who was in the US on his honeymoon, also died, Ansa reported.
Sixteen people, including 14 passengers, a tour guide and the driver, were on the bus, the Milan-based tour operator Viaggidea said.
All 14 passengers were Italian, La Repubblica reported.
Those injured, four seriously, were taking to hospitals in the area. Two are in a critical condition, La Repubblica said, citing Italy's Foreign Ministry.
US police said the truck was heading south on Interstate 380 on Wednesday morning when it entered the northbound and and hit another truck going in the opposite direction. The bus then collided with the first truck, which was owned by Xtra Lease company.