Online flight data suggested the aircraft may have experienced a very rapid loss of height and change of direction prior to slipping off the radar.
Authorities hold little hope for those onboard.
The plane was carrying 227 passengers and 12 crew of 14 nationalities.
"Ladies and gentlemen, we are deeply saddened this morning with the news on MH370,'' Malaysian Airlines CEO Ahmad Jauhari Yahya told a press conference.
The missing Australians were Mary and Rodney Burrows and Catherine and Robert Lawton, all from Brisbane. The two couples were reportedly travelling together.
Li Yuan and Gu Naijun, believed to be from Sydney, were also missing.
Two New Zealanders were also aboard the flight.
One of the Lawtons' neighbours described them as a lovely couple who enjoyed travelling.
Australians used social media sites to express hope for all the passengers' survival.
"Praying for a miracle,'' one person wrote.
The 227 passengers included 152 Chinese and one infant, 38 Malaysians, 12 Indonesians, three passengers and an infant from the US, three French, two each from Ukraine and Canada and one each from Russia, Italy, Taiwan, The Netherlands and Austria.
Australian authorities said they "feared the worst'' for all aboard flight MH370.
"Consular officials are currently in touch with Malaysian Airlines and with the families of the missing Australian passengers,'' Senator Brett Mason, parliamentary secretary to the Minister for Foreign Affairs, told reporters in Sydney.
"At the moment there is no clarity as to what has occurred.
"But can I just add that the families of the ... missing Australian passengers must be desperately concerned and the thoughts of the Australian government and I'm sure all Australians go out to them at the moment.''
As of Saturday night there had been no request for Australian authorities to join the search and rescue operation.
One of the more puzzling aspects of the incident is that the flight appeared to relay no distress signal or give other indications that it was in trouble.
It was piloted by Captain Zaharie Ahmad Shah, 53, who had flown for the airline since 1981, the carrier said.
"The plane lost contact near Ca Mau province airspace as it was preparing to transfer to Ho Chi Minh City air traffic control,'' a statement posted on the official Vietnamese government website said.
Ca Mau is located at the southernmost tip of Vietnam.
The plane's signal was never transferred to Ho Chi Minh air traffic control.
Malaysia Airlines has a good safety record. Its worst-ever crash occurred in 1977, when 93 passengers and seven crew perished in a hijacking and subsequent crash in southern Malaysia.
The Boeing 777-200 model is also said to be one of the world's most popular jets.
The long-range jumbo jet has helped connect cities at the far ends of the globe, with flights as long as 16 hours.
But more impressive is its safety record: The first fatal crash in its 19-year history only came in July 2013 when an Asiana Airlines jet landed short of the runway in San Francisco. Three of the 307 people aboard died.
There were upsetting scenes at Beijing's airport as news of flight MH370 filtered through.
Screens first indicated that the flight was "delayed'', but later updated its status to "cancelled''.
Friends and relatives of those aboard broke down in tears and were pictured making frantic telephone calls.
- AP
