There were no reports of bad weather and no sign why the Boeing 777-200ER, powered by Rolls-Royce Trent engines, would have vanished from radar screens about an hour after it took off.
By nightfall in the region, there were no signs of the plane or any wreckage, some 17 hours after it went missing.
A large number of planes and ships from several countries were scouring the area where the plane last made contact, about halfway between Malaysia and the southern tip of Vietnam.
"The search and rescue operations will continue as long as necessary," Malaysian Prime Minister Najib Razak told reporters in Kuala Lumpur. He said 15 air force aircraft, six navy ships and three coast guard vessels had been pressed into service by Malaysia.
China and the Philippines have sent ships to a region near the South China Sea to help. The United States, the Philippines and Singapore also dispatched military planes to help in the search.
China has also put other ships and aircraft on standby, said Transport Minister Yang Chuantang.
Vietnamese state media, quoting a senior naval official, had reported that the plane had crashed off south Vietnam. Malaysia's transport minister later denied any crash scene had been identified.
"We are doing everything in our power to locate the plane. We are doing everything we can to ensure every possible angle has been addressed," Transport Minister Hishamuddin Hussein told reporters near the Kuala Lumpur International Airport.
"We are looking for accurate information from the Malaysian military. They are waiting for information from the Vietnamese side," he said.
Vietnamese Admiral Ngo Van Phat later qualified his earlier remarks about a crash site having been identified and told Reuters he was referring to a presumed location beneath the plane's flight path, using information supplied by Malaysia.
A crash, if confirmed, would likely mark the US-built airliner's deadliest incident since entering service 19 years ago.
The plane, aged over 11 years, disappeared without giving a distress signal — a chilling echo of an Air France flight that crashed into the South Atlantic on June 1, 2009, killing all 228 people on board. It vanished for hours and wreckage was found only two days later.
Search and rescue vessels from the Malaysian maritime enforcement agency reached the area where the plane last made contact at about 4:30 p.m. local time (0330 ET) but saw no sign of wreckage, a Malaysian Maritime Enforcement Agency told Reuters.
Vanished after reaching 35,000 feet
Flight MH370 last had contact with air traffic controllers 120 nautical miles off the east coast of the Malaysian town of Kota Bharu, Malaysia Airlines chief executive Ahmad Jauhari Yahya said in a statement.
The airline said people from 14 nationalities were among the 227 passengers, including at least at least 152 Chinese, 38 Malaysians, seven Indonesians, six Australians, five Indians, four French and three Americans.
Chinese Foreign Minister Wang Yi told reporters in Beijing that China was "extremely worried" about the fate of the plane and those on board.
Chinese relatives of passengers angrily accused the airline of keeping them in the dark, while state media criticized the carrier's poor response.
"There's no one from the company here, we can't find a single person. They've just shut us in this room and told us to wait," said one middle-aged man at a hotel near Beijing airport where the relatives were taken.
"We want someone to show their face. They haven't even given us the passenger list," he said.
Another relative, trying to evade a throng of reporters, muttered: "They're treating us worse than dogs."
In Kuala Lumpur, Malaysia Airlines told passengers' next of kin to come to the international airport with their passports to prepare to fly to the crash site, which has still not been identified.
About 20-30 families were being kept in a holding room at the airport, where they were being guarded by security officials and kept away from reporters.
The flight left Kuala Lumpur around 12:40 a.m. (1640 GMT Friday) and was due to land in the Chinese capital at 6:30 a.m. (2230 GMT Friday) the same day.
Malaysia Airlines has one of the best safety records among full-service carriers in the Asia-Pacific region.
It identified the pilot of MH370 as Captain Zaharie Ahmad Shah, a 53-year-old Malaysian who joined the carrier in 1981 and has 18,365 hours of flight experience.
Chinese state media said 24 Chinese artists and family members, who were in Kuala Lumpur for an art exchange program, were aboard. The Sichuan provincial government said Zhang Jinquan, a well-known calligrapher, was on the flight.
If it is confirmed that the plane crashed, the loss would mark the second fatal accident involving a Boeing 777 in less than a year and by far the worst since the jet entered service in 1995.
An Asiana Airlines Boeing 777-200ER crash-landed in San Francisco in July 2013, killing three passengers and injuring more than 180.
Boeing said it was monitoring the situation but had no further comment. The flight was operating as a China Southern Airlines codeshare.