The strikes on cities including Kyiv and Dnipro followed Russian warnings of "systematic" attacks on the capital after a drone attack on a dormitory in Ukraine's Russian-held region of Luhansk last month. Kyiv denies targeting the dormitory.
It was the third heavy assault on Kyiv in under a month, but Russia has been relentlessly attacking Ukrainian cities, including Kyiv, since it invaded its smaller neighbour in 2022.
US-brokered talks on the war in Ukraine have stalled with Washington focusing on Iran, while Russian advances on the battlefield have slowed this year and Kyiv has stepped up strikes on Russian oil refineries.
Ukrainian President Volodymyr Zelenskiy said Russia had fired 73 missiles and more than 600 drones in the overnight attack and urged Washington to send additional Patriot missile interceptors to replenish Kyiv's dwindling supplies.
"This was a large-scale attack and an absolutely clear statement from Russia: if Ukraine is not protected from ballistic and other missile strikes, these attacks will continue," Zelenskiy said on Telegram.
The Kremlin said the war had entered "a new paradigm" after what it called "inhumane acts of terror" by Ukraine's military against civilians, echoing accusations Kyiv has made against Russian forces. Moscow warned last week of systematic strikes and urged foreigners to leave Kyiv.
Zelenskiy sent a letter last week to US President Donald Trump and Congress, asking for air defence systems. As of Monday, officials said he had not received a response.
Foreign Minister Andrii Sybiha urged partners to take "concrete steps" to help Ukraine and increase pressure on Russia, appealing for tougher sanctions and more military support.
"Moscow is losing on the battlefield. No number of missiles can change this. What we can change is Russia's ability to continue terror," he said on X.
The US has been Ukraine's main foreign supplier of weapons but Kyiv has also been purchasing Patriot missiles through a NATO initiative, financed by its European allies.
Moscow's war in Ukraine has killed tens of thousands of people, forced much of the population out of their homes and devastated cities, towns and villages. Russia controls about one-fifth of Ukraine.
Ukraine has also hit civilian targets during attacks on Russia or Russian-occupied areas, though on a much smaller scale. Both sides deny targeting civilians.
Photographs on Tuesday showed large explosions and smoke billowing over high-rise buildings in Kyiv, where officials said six people were killed and over 80 wounded.
Sixteen people were killed overnight, including two young boys, in the southeastern city of Dnipro, local officials said. Russia attacked the city again later on Tuesday, and at least two more people were injured.
In Kyiv, at least nine high-rise buildings, a kindergarten, a clinic, offices and administrative buildings were damaged, and the attack temporarily cut power to 140,000 residents, power company DTEK said.
More than 40,000 took shelter in the Kyiv subway system - the biggest number in recent years. Some carried pets, belongings and mattresses.
Ukraine's Air Force said the attack included 33 hard-to-shoot-down ballistic missiles and eight Zircon hypersonic missiles, which appeared to be the largest number of such missiles used at once during the war.
The Zircon has a range of 1000 km and travels at nine times the speed of sound, Moscow says. Ukrainian Air Force units shot down or neutralised 40 missiles and 602 drones, but no Zircon was listed among them.
Russia's defence ministry said it had carried out a "massive strike" on defence industry facilities using high-precision long-range weapons, and that its strikes had hit 10 military production facilities in Kyiv.
12°C