"Russian invaders destroyed the flagship of the Ukrainian aviation, the AN-225" at the Antonov airport in Gostomel near Kyiv, the group said in a statement.
The aircraft was unique to the world, at 84 meters long (276 feet) it could transport up to 250 tonnes (551,000 pounds) of cargo at a speed of up to 850 kilometres per hour (528 mph).
It had been named "Mriya", which means "dream" in Ukrainian.
"This was the world's largest aircraft, AN-225 'Mriya'" Ukraine' Foreign Minister Dmytro Kuleba tweeted Sunday.
"Russia may have destroyed our 'Mriya'. But they will never be able to destroy our dream of a strong, free and democratic European state. We shall prevail!", he added.
Gostomel airport has seen violent clashes since the start of Russia's invasion, launched by President Vladimir Putin Thursday.
The Russian army has said it is trying to seize strategic infrastructure.
Weapons manufacturer Ukroboronprom estimated that restoring the "Mriya" would cost over $3 billion (2.7 billion euros) and could take over five years.
"Our mission is to ensure that these expenses are covered by Russia, which deliberately inflicted damage on Ukraine's aviation," the group said.
Initially built as part of the Soviet aeronautical program, the An-225 made its first flight in 1988.
After years of not flying after the fall of the Soviet Union, the only existing copy made a test flight in 2001 in Gostomel, about 20 kilometres from Kyiv.
It has been operated by Ukraine's Antonov Airlines for cargo flights and was in high demand during the start of the Covid-19 pandemic.
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