The airline will operate seven flights per week using Airbus A321s with services meeting four-star standards.
The flights will take a total of four hours and a half, departing at 00:20 from Da Nang and 9:30 from Osaka.
This will be the 11th air route to Japan that Vietnam Airlines operates, along with those from Hanoi, Ho Chi Minh City and Da Nang to Tokyo, Osaka, Nagoya, and Fukuoka.
For the opening occasion, the airline will launch a ticket promotion programme from September 30, offering fares from VND5.89 million (US$249) for flights between October 28 to December 31, as well as adding reward points for its loyal customers.
Vietnam Airlines is currently the largest carrier amongst those operating routes between Vietnam and Japan, with 70 flights per week on average.
Since the first direct flight on the Vietnam-Japan route took off in 1994, Vietnam Airlines has carried 11.3 million passengers between the two countries, accounting for 65% of the market share.