"At the moment we have no idea where this aircraft is right now," Malaysia Airlines Vice President of Operations Control Fuad Sharuji told CNN's "AC360."
The airline said in a statement that Subang Air Traffic Control in Malaysia lost contact with Flight MH370 at 2:40 a.m. (1:40 p.m. ET Friday).
The Boeing 777-200 departed Kuala Lumpur at 12:41 a.m. and was expected to land in Beijing at 6:30 a.m., a 2,300-mile (3,700 kilometer) trip.
It was carrying 227 passengers, two of them infants, and 12 crew members, it said.
The jet was carrying about 7.5 hours of fuel and would likely have run out of fuel, Sharuji said.
"Malaysia Airlines is currently working with the authorities who have activated their Search and Rescue team to locate the aircraft," the statement said. The public can call +603 7884 1234 for further information.
Efforts to contact the plane had been fruitless.
"We're closely monitoring reports on Malaysia flight MH370," Boeing said in a tweet. "Our thoughts are with everyone on board."
"It doesn't sound very good," retired American Airlines Capt. Jim Tilmon told CNN's "AC360." He noted that the route is mostly overland, which means that there would be plenty of antennae, radar and radios to contact the plane.
"I've been trying to come up with every scenario that I could just to explain this away, but I haven't been very successful."
He said the plane is "about as sophisticated as any commercial airplane could possibly be," with an excellent safety record.
There is one recent blemish: An Asiana Airlines Boeing 777 carrying 291 passengers struck a seawall at San Francisco International Airport in July 2013, killing three people and wounding dozens more.
Malaysia Airlines operates in Southeast Asia, East Asia, South Asia, the Middle East and on the route between Europe and Australasia.
The airline's roots date back to 1937, when it operated passenger and cargo flights in Malaysia.
In April 1942, it was incorporated as Malaysia Airways Limited; it later became Malaysia Airlines.
The airline has its headquarters and registered office at Sultan Abdul Aziz Shah Airport in Subang, Malaysia, and its main airline hub is at Kuala Lumpur International Airport, according to itswebsite.
By Tom Watkins and Chelsea J. Carter, CNN
updated 8:39 PM EST, Fri March 7, 2014