Malaysia Airlines says it has lost contact with a plane travelling from Kuala Lumpur to Beijing, with 239 people on board.
The airline said in a statement that flight MH370 disappeared at 02:40 local time on Saturday (18:40 GMT on Friday).
It had been expected to land in Beijing at 06:30 (22:30 GMT).
The plane went off the radar south of Vietnam, according to a statement on the Vietnamese government website.
Its last known location was off the country's Ca Mau peninsular although the exact position was not clear, it said.
Malaysia Airlines said it was "currently working with the authorities who have activated their search and rescue team to locate the aircraft".
"Our team is currently calling the next-of-kin of passengers and crew."
The Boeing B777-200 aircraft was carrying 227 passengers, including two children, and 12 crew members.
In a brief press conference on Saturday, Malaysia Airlines chief executive Ahmad Jauhari Yahya said the company was still working to establish the location of the plane.
He said the company was "deeply saddened" at the situation and that it would provide regular updates.
'Very worried'
The passengers were of 14 different nationalities, he added.
Among them were 152 Chinese nationals, 38 Malaysians, 12 people from Indonesia and six from Australia.
The pilot was Capt Zaharie Ahmad Shah, 53, who joined Malaysia Airlines in 1981, Mr Yahya said.
The flight went missing two hours after taking off from Kuala Lumpur.
The aircraft did not enter airspace controlled by China and did not make contact with Chinese controllers, China's state-run Xinhua news agency said.
A Vietnamese navy official told the BBC that the plane had gone missing within Malaysian maritime territory.
Officials have refused to confirm that the aircraft has crashed.
Meanwhile, China has sent two ships to the South China Sea to help in any rescue, Chinese state television said.
Chinese Premier Li Keqiang is reported to have told government departments to "start the emergency procedures, strengthen communication with Malaysian Civil Aviation authorities, prepare search and rescue efforts", says the BBC's John Sudworth in Beijing.
The flight has now been removed from the international arrivals board at Beijing International Airport, our correspondent reports from the terminal. It had been listed as delayed for more than six hours after it was due.
Friends and relatives expecting to meet passengers from the flight have been instructed to go to a nearby hotel where officials are on hand to provide support, our correspondent adds.
The Associated Press reported a woman weeping on a shuttle bus who was heard to say on a mobile phone: "They want us to go to the hotel. It cannot be good."
"This news has made us all very worried," Chinese Foreign Minister Wang Yi said.
"We hope every one of the passengers is safe. We are doing all we can to get more details."
Fuad Sharuji, Malaysian Airlines' vice-president of operations control, told CNN the plane had been flying at an altitude of 35,000ft (10,700m) and that the pilots had not reported any problems with the aircraft.
"Our thoughts and prayers are with all affected passengers and crew and their family members," Malaysia Airlines said.
The airline is the national carrier of Malaysia and one of Asia's largest, flying nearly 37,000 passengers daily to some 80 destinations worldwide.
The route between Kuala Lumpur to Beijing has become more and more popular as Malaysia and China increase trade, says the BBC's Jennifer Pak in Kuala Lumpur.
The Boeing 777 had not had a fatal crash in its 20-year history until an Asiana plane came down at San Francisco airport in July 2013. Three teenage girls from China died in that incident.
Boeing said in a statement posted on Twitter: "We're closely monitoring reports on Malaysia flight MH370. Our thoughts are with everyone on board."