The Kremlin on Monday warned the United States of "consequences" and summoned its ambassador after Moscow said a Ukrainian strike with a US missile on Crimea killed four people.
Moscow has increasingly blasted Washington and Kyiv's Western backers for supplying weapons to be fired on Russian targets, calling them direct participants in the two-year conflict.
Kremlin spokesman Dmitry Peskov called Sunday's strike on Sevastopol "barbaric" and accused Washington of "killing Russian children".
Two of the victims were minors, Sevastopol governor Mikhail Razvozhayev wrote on Telegram.
Peskov also pointed to comments by President Vladimir Putin earlier this month about arming countries to potentially strike Western targets.
"The involvement of the United States, the direct involvement, as a result of which Russian civilians are killed, cannot be without consequences," Peskov told reporters on Monday.
"Time will tell what these will be," he said.
"Just ask my colleagues in Europe and above all in Washington, ask the press secretaries there why their government is killing Russian children," he said.
The foreign ministry said it had summoned US envoy Lynne Tracy.
It later issued a statement saying that Washington "bears equal responsibility with the Kyiv regime for this atrocity" and the strike would "not go unpunished".
Russia said the strike on Sunday was carried out with a US-supplied ATACMS missile loaded with a cluster warhead.
Local Moscow-installed officials said the missile hit an area of the port city with sandy beaches and hotels.
Russia said 82 people including 27 children were hospitalised with injuries from the strike.
Health Minister Mikhail Murashko was quoted by TASS news agency as saying on Monday that 14 of the injured were in a serious condition.
At a meeting with international news agencies including AFP this month, Putin criticised the West's delivery of long-range weapons to Ukraine.
"Why don't we have the right to supply weapons of the same class to regions of the world where there will be strikes on sensitive facilities of those (Western) countries?" Putin said.
"That is, the response can be asymmetric. We will think about it," he told reporters.
Peskov also referred back to comments by Putin that target data for Ukrainian strikes was being provided by Western countries.
Russia unilaterally annexed Crimea in 2014.
Andriy Yermak, the head of the Ukrainian president's office, said on Monday: "Crimea is Ukraine."
"Russia must leave the peninsula. Their army and military objects there must cease to exist," he said on social media.
A senior aide to the Ukrainian president, Mykhailo Podolyak, also suggested that Crimea was a legitimate military target.
"Crimea is also a large military camp and warehouse, with hundreds of direct military targets, which the Russians are cynically trying to hide and cover up with their own civilians," he said.
Russia has been launching deadly strikes against Ukraine on a daily basis since it began its campaign in February 2022.
Ukraine says 551 children have been killed and 1,396 injured since the start of the assault.