Ukraine had anticipated the overnight attack, with President Volodymyr Zelenskiy warning the previous day that intelligence services had concluded that Russia was building up for a "massive" strike.
Although Ukraine knew about the looming attack, which coincided with Russian President Vladimir Putin's 74th birthday, it could not fend it off completely.
The deaths and damage illustrated the difficulty Ukraine has in countering Russia's ballistic missiles and the new jet-powered drones used in Moscow's escalating bombardments.
Without ammunition for its US-made Patriot air defence systems, Ukraine cannot stop Russian ballistic weapons.
It is racing to develop a new generation of interceptors fast enough to catch Moscow's high-flying jet-propelled drones.
Russia and Ukraine are engaged in a long-range aerial war as their armies remain largely deadlocked on the battlefield, more than four-and-a-half years after Moscow's all-out invasion of its neighbour.
The unrelenting aerial attacks are hurting Russia but could be ruinous for smaller Ukraine.
US-led peace efforts appear unlikely to bring any short-term relief, with the possibility of holding low-level technical talks still under discussion.
Putin, meanwhile, is pressing ahead with the invasion in the belief that Ukrainians will buckle under the pressure and Kyiv's Western supporters will not stay the course, Western analysts say.
A Russian strike destroyed an apartment block in Pryluky, in Ukraine's northern Chernihiv region, killing 13 people, including four children, and wounding about 50, Interior Minister Ihor Vyhivskyi said.
Deaths were also reported in three other Ukrainian cities, including the capital Kyiv, according to Zelenskiy.
"The Russians wanted to strike painfully and demonstratively," the Ukrainian leader said on social media.
Ukraine is looking worldwide for available Patriot missiles, which are in short supply due to the Iran war.
"Russian ballistic missiles remain the greatest challenge. And air defence packages for us right now are a vital necessity," Zelenskiy said.
In Kremenchuk, in the Poltava region, two people were killed and seven injured, said Vitalii Diakivnych, head of the regional military administration, and a rescue operation was continuing.
"That is exactly what the enemy is counting on. For us to be afraid to fall asleep. To let our children out of our sight. To plan anything. So that everyone thinks: next time it could be my address," he said.
Russia's defence ministry said the military carried out a massive strike overnight targeting industrial facilities involved in the production and storage of missiles and drones across Ukraine.
The ministry said that port and ship repair facilities in the southern Odesa region and ships carrying cargo for the Ukrainian military were also hit.
Ukraine has hit back at Russia by launching long-range drones and missiles at oil refineries and storage depots.
Zelenskiy said on Wednesday that Ukraine targeted two oil facilities and a training ground in the Perm, Samara, and Astrakhan regions of Russia.
Russian officials made no immediate comment.
Zelenskiy also indicated that Ukraine had struck in the Black Sea.
He posted images of a fire said to show an oil tanker burning in the water near the Russian city of Sochi.
Unconfirmed media reports said it was carrying oil from Novorossiysk to India and was attacked by Ukrainian sea drones.
