Three will be three flights a week on Tuesday, Friday and Saturday between Hanoi and Milan, the airline said in a statement Tuesday.
Round-trip tickets are priced between VND14.8 million and VND17.3 million (US$600-700), with flights serviced by Boeing 787 widebody aircraft.
Vietnam Airlines will be the only carrier offering a direct route between the two countries. It also has plans to launch a route connecting Ho Chi Minh City to Milan after 2025.
Milan is the second biggest city in Italy behind Rome. Last year, Vietnam welcomed 81,000 visitors from Italy.
With the addition of the Hanoi-Milan route, Vietnam Airlines will have nine Vietnam-Europe routes, including flights to Paris, Frankfurt, and London.
A new direct route between Hanoi/HCMC and Munich is also slated for launch in October.