The flight departed Kuala Lumpur International Airport at 00:41, 8 March Malaysia time (16:41, 7 March UTC) and was last seen on ATC radar at 6°55′15″N 103°34′43″E (approximately 180 km/100 mi NNE of Kuala Terengganu, Malaysia). The aircraft ceased all communications and the transponder signal was lost right before it was passed off to the Ho Chi Minh Area Control Center.
The Aviation Herald reported that Subang Air Traffic Control lost radar and radio contact with the aircraft at 01:22 and officially advised Malaysia Airlines at 02:40 that the aircraft was missing. However, a Malaysia Airlines spokesperson said that the last conversation between the flight crew and air traffic control in Malaysia had been around 01:30, and stated that the plane had not disappeared from air traffic control systems in Subang until 02:40, which is long enough for the plane to have been flying across Vietnam.
Malaysia Airlines issued a media release stating that contact was lost at 02:40 when the aircraft was approximately 120 nautical miles (220 km) east of Kota Bharu at the South China Sea, which is the border of Malaysian and Vietnamese airspace. The plane relayed no distress signal, indications of bad weather or technical problems before vanishing from radar screens. The flight was scheduled to land at Beijing Capital International Airport at 06:30. When radar contact with the aircraft was lost, it was carrying enough fuel for an additional 7.5 hours of flying time. Relevant authorities in China and Thailand informed their Malaysian counterparts that the aircraft had not entered their airspace.
According to Admiral Ngo Van Phat of the Vietnam People's Navy, military radar lost the plane "some 153 nautical miles (300 km)" south of Thổ Chu in the Gulf of Thailand. The Vietnamese government initially reported that the aircraft had crashed at sea in the Gulf of Thailand, although the airline denied this claim, and the claim about the known location of the aircraft by the Vietnamese Navy was rejected by Malaysian Minister of Transport, Hishammuddin Hussein. The Vietnamese Navy later clarified that the admiral had actually been referring to the location where contact was last made, rather than indicating a crash site.