Ukraine accused "terrorists" - militants fighting to unite eastern Ukraine with Russia - of shooting down the Malaysia Airlines Boeing 777 with a heavy, Soviet-era SA-11 ground-to-air missile as it flew from Amsterdam to Kuala Lumpur.
Leaders of the rebel Donetsk People's Republic denied any involvement, although around the same time their military commander said his forces had downed a much smaller Ukrainian transport plane. It would be their third such kill this week.
The scale of the disaster affecting scores of foreigners could prove a turning point for international pressure to resolve a crisis that has claimed hundreds of lives in Ukraine since pro-Western protests toppled the Moscow-backed president in Kiev in February and Russia annexed Crimea a month later.
Reuters journalists saw burning and charred wreckage bearing the red and blue Malaysia insignia and dozens of bodies strewn in fields near the village of Hrabove, 40 km (25 miles) from the Russian border near the rebel-held regional capital of Donetsk.
Despite the shooting down of several Ukrainian military aircraft in the area in recent months, including two this week, and renewed accusations from Kiev that Russian forces were taking a direct part, international air lanes had remained open.
MAS said air traffic controllers lost contact with flight MH-17 at 1415 GMT as it flew over eastern Ukraine towards the Russian border, bound for Asia with 280 passengers and 15 crew aboard.
Flight tracking data indicated it was at its cruising altitude of 33,000 feet when it disappeared.
That would be beyond the range of smaller rockets used by the rebels to bring down helicopters and other low-flying Ukrainian military aircraft - but not of the SA-11 system which a Ukrainian official accused Russia of supplying to the rebels.
"I was working in the field on my tractor when I heard the sound of a plane and then a bang," one local man at told Reuters at Hrabove, known in Russian as Grabovo.
"Then I saw the plane hit the ground and break in two. There was thick black smoke."
An emergency worker said at least 100 bodies had been found so far and that debris was spread over 15km.
People were scouring the area for the black box flight recorders and separatists were later quoted as saying they had found one.
"MH-17 is not an incident or catastrophe, it is a terrorist attack," Ukrainian President Petro Poroshenko tweeted.
The loss of MH17 is the second disaster for Malaysia Airlines this year, following the mysterious loss of flight MH370.
It disappeared in March with 239 passengers and crew on board on its way from Kuala Lumpur to Beijing.
HRABOVE, Ukraine (Reuters): A Malaysia Airlines plane was brought down over eastern Ukraine on Thursday, killing all 295 people aboard and sharply raising the stakes in a conflict between Kiev and pro-Moscow rebels in which Russia and the West back opposing sides.