Vice President Joe Biden said the incident was "not an accident" and described the Malaysia Airlines plane as having been "blown out of the sky."
Among the unanswered questions was whether the missile was launched from the Russian or Ukrainian side of the border they share, according to the official, who was not authorized to discuss the matter publicly by name and insisted on anonymity. But the official said U.S. intelligence assessments suggest it is more likely pro-Russian separatists or the Russians rather than Ukrainian government forces shot down the plane.
The U.S. has sophisticated technologies that can detect missile launches, including the identification of heat from a rocket engine.
President Barack Obama, speaking during a trip to Delaware, made no mention of who might be responsible for the crash of the plane carrying 298 people, and called the incident a "terrible tragedy."
Following the crash, the Federal Aviation Administration said U.S. airlines voluntarily agreed not to operate near the Ukraine-Russia border. The agency said it was monitoring the situation to determine whether further guidance was necessary.
A global air safety group said an international coalition of countries should lead the investigation of the crash. Safety experts say they're concerned that because the plane crashed in area of Ukraine that is in dispute, political considerations could affect the investigation.
Kenneth Quinn of the Flight Safety Foundation said only "an independent, multinational investigation can truly get to the bottom of it without political interference."
The incident came one day after Obama levied broad economic sanctions on Russia as punishment for its threatening moves in Ukraine. Moscow is widely believed to be supporting pro-Russian separatists fomenting instability near the border, though the Kremlin denies those assertions.
Obama discussed the new sanctions by phone Thursday with Russian President Vladimir Putin. The White House said reports of the downed plane surfaced during that call and Putin mentioned the incident to his American counterpart.
Speaking later during a trip to Delaware, Obama said "the world is watching" the deadly incident.
"It looks like it might be a terrible tragedy," he said. "Right now we're working to determine whether there were American citizens on board. That is our first priority."
Secretary of State John Kerry said late Thursday that authorities still were trying to determine whether any Americans had been on the plane.
Obama went ahead later Thursday with a scheduled evening of fundraising for Democrats in New York, but called Ukrainian President Petro Poroshenko as he traveled to the events. The White House said Obama and Poroshenko agreed that all evidence from the crash site must remain in Ukraine until international investigators were able to examine it.
The president also called both Prime Minister Najib Razak of Malaysia and Prime Minister Mark Rutte of the Netherlands, where the flight originated. Officials said Obama and Rutte discussed the need for international investigators to have immediate access to the crash site.
The U.S. planned to send a team of experts to Ukraine to assist with the investigation.
Anton Gerashenko, an adviser to Ukraine's interior minister, said on his Facebook page that the plane was flying at an altitude of 33,000 feet when it was hit by a missile fired from a Buk launcher.
U.S. officials said Russia has sent a wide range of heavy weaponry into eastern Ukraine in recent months, although it is uncertain whether that includes the Buk air defense system, which is operated by a tracked vehicle. The U.S. suspects that Russian shoulder-fired anti-aircraft weapons have been provided to the separatists.
According to a Ukrainian state-owned import-export firm that specializes in military technology and weaponry, known as Ukroboronservice, the Ukrainian military operates the Buk-M1 system, which is designated by NATO as the SA-11 Gadfly. It is designed to shoot down military aircraft, including helicopters, as well as cruise missiles.
The Russians also are believed by U.S. officials to have provided the separatists in eastern Ukraine with other heavy weaponry such as artillery, multiple-launch rocket systems, tanks and armored personnel carriers.
The Federal Aviation Administration had previously warned U.S. pilots earlier this year not to fly over portions of the Ukraine in the Crimea region, according to notices posted on the agency's website.
The notices were posted on April 23. The U.N.'s International Civil Aviation Organization and the aviation authorities in most countries issue similar notices for areas where unrest or military conflict creates a risk of being shot down.