Russia's hours-long overnight barrage killed four people and wounded more than 80, according to Ukrainian officials, and officials said dozens of residential buildings and several schools had been damaged.
"It was a terrible night for Kyiv," Kyiv Mayor Vitali Klitschko said in a Telegram message from the site of one attack on Sunday.
"Right now, rescuers are putting out fires and clearing debris. Medics are providing assistance to the victims."
It was only the third time Russia has used the Oreshnik missile against Ukraine since the war began with Russia's full-scale invasion in February 2022.
The Oreshnik has a range of several thousand kilometres and is capable of carrying a nuclear warhead.
The previous two strikes had hit major cities, but Zelenskiy said this one had struck Bila Tserkva, a city of 200,000 people about 65 km from the outskirts of Kyiv.
In total, the air force said, Russia launched 90 missiles and 600 drones.
"It's important that this does not remain without consequences for Russia," Zelenskiy said on the Telegram messaging app.
"Decisions are needed – from the United States, from Europe and others."
Zelenskiy said Russia had also targeted water-supply facilities, saying Moscow wanted to damage them before the summer increased demand.
Russia said it had used Oreshnik, Iskander, Kinzhal and Zircon missiles in retaliation for Kyiv's strikes on civilian targets in Russia. Ukraine says it does not target civilians.
Interfax news agency cited the Russian Defence Ministry as saying the strikes targeted Ukrainian military command facilities, including sites used by land forces and military intelligence, air bases and military-industrial sites.
Moscow also denies targeting civilians, although thousands have been killed by its bombardments of Ukrainian cities during the war.
Explosions reverberated through Kyiv just after 1am, following a warning by Ukraine's air force on its Telegram channel that Russia might launch an Oreshnik.
Windows were blown out in Ukraine's Foreign Ministry building and some damage was reported in Kyiv's historic Independence Square.
At least two people were killed and another 69 wounded in the capital, Klitschko said.
Many residents sought shelter overnight in the city's metro stations. Nataliia Zvarych, 62, said she had rushed to her local station as explosions started rocking the city.
"It was terrifying, scary," she said. "We have been sitting here for more than three hours now, listening to the explosions up there."
Strikes were reported in other parts of Ukraine. Two people were killed and nine others injured in attacks on the broader Kyiv region, said regional governor Mykola Kalashnyk.
And 11 people were wounded in the central Ukrainian city of Cherkasy when a drone crashed into an apartment block, Prime Minister Yuliia Svyrydenko said.
As the sun rose in Kyiv on Sunday, black smoke from several fires drifted across the skyline, leaving an acrid smell in parts of the city.
Firefighters used hoses to douse the flames in damaged buildings while rescue workers evacuated the wounded.
The front facade of one five-storey residential building had collapsed, images showed.
Officials reported damage to offices, shops, warehouses and the foyer of a metro station.
Zelenskiy had warned on Saturday that Russia was preparing a strike using the Oreshnik, citing intelligence from Ukraine, the US and Europe.
Russian President Vladimir Putin has said in the past that the missile is impossible to intercept because of its reported velocity of more than 10 times the speed of sound.
