The daily route is being flown by the short-to-medium range commercial passenger jet Airbus 321, which will make the 1,000km journey between the two capitals in about one hour.
The direct flight will also help boost the social and economic relations between the two countries, according to CA Air's CEO Trinh Hong Quang.
CA Air's CEO Hong Quang said the new route is part of the airline's master plan to expand its networks.
Other new routes include Siem Reap - Bangkok , Siem Reap - Hanoi and Phnom Penh - Bangkok . Direct flights to Hong Kong, Seoul and Singapore are under consideration, Quang added.
The flight frequency between Phnom Penh and Ho Chi Minh City is also being increased.
The Phnom Penh-based airline, a 51/49 joint venture between the Cambodian Government and Vietnam 's flag carrier Vietnam Airlines, currently has 11 flight routes including three domestic flights and eight international flights.
After three years of operation, CA Air, which possesses five aircraft including three A320 jets, has registered 5,570 safe flights.
It transported 325,000 passengers in 2012, up 6 percent compared to the previous year with a seat occupancy rate of 68 percent.
CA Air plans to have 10,500 flights and carry 754,000 passengers in 2013.
