President Volodymyr Zelenskiy said the vessel carrying Ukrainian grain to Egypt had been hit overnight by a Russian missile just after it left Ukrainian territorial waters.
There were no casualties, he said.
There was no immediate comment from Russia.
Ukrainian Foreign Minister Andrii Sybiha said the strike was "a brazen attack on freedom of navigation and global food security".
Ukraine's navy said Russian Tupolev Tu-22 bombers had fired a number of cruise missiles at 11.02pm on Wednesday.
It was the first time a missile has struck a civilian vessel transporting grains at sea since the start of Russia's invasion in February 2022.
Some vessels have been damaged during Russian attacks on Ukrainian ports where they were moored.
The incident comes as Zelenskiy has been trying to court the "Global South," including countries such as Egypt - the destination of the grain according to Ukraine - and convince them to support Ukraine in the war.
The strike comes as NATO allies are considering allowing Ukraine to make deeper strikes into Russia, a step officials in Moscow have warned will elicit a response.
The US and several of its allies have accused Iran of a major escalation by supplying ballistic missiles to Russia.
UK maritime security company Ambrey said in a note that a Saint Kitts and Nevis-flagged bulk carrier had been struck by a Russian-launched missile after leaving the Ukrainian port of Chornomorsk in Ukraine's Odesa region.
The vessel sustained damage to its port side, including a cargo hold and a crane, it said.
Ukrainian officials say three Red Cross workers were killed in a Russian strike in Donetsk. (AP PHOTO)
The navy identified the vessel as the Aya bulk carrier.
Ship tracking data showed the vessel's last reported position was off the Romanian port of Constanta.
Zelenskiy posted images showing the twisted metal of a crane and other damage.
An industry source told Reuters the strike had taken place not far from the mouth of the Danube river.
Dmytro Pletenchuk, spokesman for Ukraine's navy, told Reuters the vessel was in Romania's maritime economic zone.
A country's maritime economic zone is an area that extends beyond its territorial waters.
Romania's naval authority said the vessel had not been in its territorial waters and that its assistance had not been requested in any way.
Zelenskiy wrote on X: "We are waiting for the world to react. Wheat and food security should never be targets for missiles."
Ukraine is a major global grain exporter that has had to battle Russia in the Black Sea to revive its exports through its sea ports since Russia's invasion imposed a de facto blockade.
The exports were revived later in 2022 - albeit with smaller volumes - from the three ports of greater Odesa under a deal mediated by the United Nations and Turkey that broke down last year.
In August 2023, Ukraine established its own shipping corridor - without Russia's blessing - after using naval drones and long-range weapons to strike back at Russia's Black Sea Fleet and push its vessels away from the west of the sea.
The shipping corridor hugs the western coast of the Black Sea before exiting Ukrainian waters and south past Romania and Bulgaria.
Zelenskiy also accused Russian forces in the eastern Donetsk region of having attacked vehicles of the International Committee of the Red Cross on Thursday.
"Unfortunately, three people were killed in this Russian strike," Zelenskiy wrote on X.
Two people were injured in the attack, he said.
The Ukrainian president also published an image showing a Red Cross lorry up in flames.
"In this war, everything is absolutely clear - Russia sows evil, Ukraine defends life," Zelenskiy wrote.
with DPA
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