The early Friday morning attacks followed a warning from Russian President Vladimir Putin, conveyed via US President Donald Trump, that the Kremlin would hit back after Ukrainian drones destroyed several strategic bomber aircraft in attacks deep inside Russia.
Zelenskiy said three emergency responders were killed in the missile and drone salvo against the capital. Another person died in an attack on the northwestern city of Lutsk.
"Those killed in Kyiv were rescue workers who arrived at the scene of an initial strike and, unfortunately, were killed in a repeat Russian strike," Zelenskiy said in his nightly video address.
Foreign Minister Andrii Sybiha, writing on X, said Russia had "'responded' to its destroyed aircraft... by attacking civilians in Ukraine.... Multi-storey buildings hit. Energy infrastructure damaged."
Russia's Defence Ministry said its forces had carried out the strike on military and military-related targets in response to what it called Ukrainian "terrorist acts" against Russia.
Zelenskiy said 80 people nationwide had been injured in the attacks, which also struck several other towns and cities. He said residents could still be trapped under rubble.
In Lutsk, the national emergency service said 30 people were injured in addition to the one death. Prosecutors said the attack damaged private homes, educational institutions and a government building.
Russian forces also struck industrial facilities and infrastructure in the western city of Ternopil, leaving parts of it without power, Mayor Serhii Nadal said.
The regional administration said the attack had injured 10 people and asked residents to temporarily stay inside due to a high concentration of toxic substances in the air after a fire.
The air force said Russia had used 407 drones, one of the largest numbers recorded in a single attack. Forty-five cruise and ballistic missiles were also fired, it said.
Kyiv's metro transport system was disrupted by a Russian strike that hit and damaged tracks between stations, the military administration said. The state rail company said it was also diverting some trains due to rail damage outside the city.
Reuters witnesses reported a series of booming explosions powerful enough to rattle windows far from the impact sites.
Some Kyiv residents sought shelter in metro stations, or in underground car parks.
In the capital's Solomianskyi district, a Russian drone slammed into the side of an apartment building, leaving a gaping hole and burn marks, a Reuters photographer at the scene said.
Falling concrete blocks from the building crushed cars parked below. Two police investigators were examining what appeared to be the drone's engine.
Earlier in the night, Reuters reporters heard the sound of Russian kamikaze drones buzzing in the sky, accompanied by the sounds of outgoing fire from Ukrainian anti-aircraft batteries.
Zelenskiy called for concerted pressure on Russia.
"If someone is not applying pressure and is giving the war more time to take lives – that is complicity and accountability. We must act decisively," he wrote on X.
The Ukrainian military said it had launched a pre-emptive strike overnight on the Engels and Dyagilevo airfields in the Russian regions of Saratov and Ryazan, in addition to striking at least three fuel reservoirs.
In one of the most audacious attacks of the three-year-old war between Ukraine and Russia, Ukrainian spies last weekend destroyed some of Russia's strategic bomber aircraft on the ground using quadrocopter drones hidden in wooden sheds.
After a phone conversation with Putin on Wednesday, Trump said the Kremlin was planning an unspecified response to the Ukrainian attack on the Russian air bases.
