Airline officials admitted they were gravely concerned for the safety of the aircraft, which was carrying four Americans and seven Australians, as well as passengers from France and China.
Crying relatives of Chinese passengers on board the plane wept at Beijing airport as it became clear the jet had probably crashed.
An unconfirmed report on a flight tracking website said the aircraft had plunged 650ft and changed course shortly before all contact was lost.
The route would have taken flight MH370, a B777-200 aircraft, across the Malaysian mainland in a north-easterly direction and then across the Gulf of Thailand.
Those on board included two infants and 12 crew members, Malaysian Airlines said in a statement, adding it was working with all authorities in the region and search and rescue teams had been mobilized.
As well as the American and Australian passengers, the aircraft was carrying 153 Chinese, 38 Malaysians, 12 Indonesians and 32 people from France.
The aircraft had been due to land in Beijing at 6.30am local time but at 7.54am the airline issued a statement saying it had not landed and was officially missing.
Tragic: Distressed relatives wait for news of the Malaysia Airlines plane which was due to land in Beijing
Grief: Family and friends waiting for the plane to arrive break down as they hear the jet has gone missing
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