The airline said flight MH370 disappeared at 2:40 am local time (1840 GMT Friday), about two hours after leaving Kuala Lumpur International Airport. It had been due to arrive in Beijing at 6:30 am local time (2230 GMT Friday).
It was carrying 227 passengers, including two infants, from 13 different nationalities, and 12 crew members.
China's state television said 158 of the passengers were Chinese.
"We deeply regret that we have lost all contacts with flight MH370 which departed Kuala Lumpur at 12.41 am earlier this morning bound for Beijing," Malaysia Airlines Group Chief Executive Officer Ahmad Jauhari Yahya said in a statement.
The statement said the Malaysian flag carrier was working with authorities, who had launched an effort to locate the aircraft.
"Our team is currently calling the next-of-kin of passengers and crew," Ahmad Jauhari said.
The plane was a Boeing 777-200. The airline's Kuala Lumpur-Beijing route passes roughly over the Indochinese peninsula.
A Malaysian Airlines spokeswoman said she could not immediately provide further details.
"This news has made us all very worried," Chinese Foreign Minister Wang Yi said in a statement.
"We hope every one of the passengers is safe. We are doing all we can to get more details."
'Contact lost over Vietnam airspace'
A report by China's Xinhua news agency said contact was lost with the plane while it was over Vietnamese airspace.
A Beijing airport spokeswoman said the facility had activated an emergency response system. Screens at the airport indicated the flight was "delayed".