Ukrainian officials told U.S. Embassy officials that everyone was "believed dead" and that debris was spread out over a 10-mile path near the town of Shakhtars'k in eastern Ukraine.
The Boeing 777 plane -- Flight MH17 from Amsterdam to Kuala Lampur with 280 passengers and 15 crew members on board -- had its "last known position was over Ukraine airspace," the airline said.
A statement from the Foreign Ministry in Kiev said the plane had been "shot down."
"According to the General Staff of Ukrainian Armed Forces, the airplane was shot down by the Russian Buk missile system as the liner was flying at an altitude of 10,000 meters [33,000 feet]," the statement added. "Ukraine has no long-range air defense missile systems in this area. The plane was shot down, because the Russian air defense systems was affording protection to Russian mercenaries and terrorists in this area. Ukraine will present the evidence of Russian military involvement into the Boeing crash."
The plane had left Amsterdam at 12:15 p.m. (local time) and was estimated to arrive in Kuala Lampur International Airport on Friday at 6:10 a.m. (local time), according to Malaysia Airlines.
Ukrainian President Petro Poroshenko said, "In recent days, this is the third tragic accident after the Russian territory were downed aircraft AN-26 and SU-25 Armed Forces of Ukraine. We do not exclude that this aircraft was also shot down, and stress that the Armed Forces of Ukraine did not commit any action to defeat the purposes of the air."
In a tweet, Russian President Vladimir Putin said, "Condolences to Malaysian Prime Minister Najib Razak in connection with the crash of a passenger aircraft in Ukraine."
President Obama, at an event in Delaware this afternoon, said, "Obviously, the world is watching reports of a downed passenger jet near the Russia-Ukraine border. And it looks like it may be a terrible tragedy. Right now, we're working to determine whether there were American citizens on board. That is our first priority, and I've directed my national security team to stay in close contact with the Ukrainian government."
He added that the U.S. "will offer any assistance we can to help determine what happened and why. And as a country, our thoughts and prayers are with all the families of the passengers, wherever they call home."
This is the second Malaysia Air plane to be involved in a crash this year.
On March 8, Malaysia Air Flight MH370 vanished with 239 people on board after it took off from Kuala Lampur bound for Beijing. Malaysian officials said the plane disappeared somewhere in the Southern Indian Ocean, but no wreckage has ever been recovered.
For more information follow ABC News reports here.