Mayor Vitali Klitschko said the overnight attack caused fires in several districts across the Ukrainian capital, damaging at least 14 high-rise buildings, a dorm, a school, a clinic, warehouses and other sites.
"Kyiv was exploding and burning," Katarina Mathernova, the EU ambassador to Ukraine, said in a social media post.
The state emergency services said 35 people were injured in the capital.
Explosions reverberated across the city as Russia kept menacing it with jet-powered drones into Tuesday afternoon.
Two people were killed in a strike on a warehouse, bringing the total death toll in the city to five, Klitschko said. Close to 30 people have been injured, authorities said.
In a separate strike, a Russian drone partially destroyed a Ukrainian TV channel building in Kyiv, President Volodymyr Zelenskiy said.
US envoys Jared Kushner and Steve Witkoff left Kyiv on Sunday following talks with Zelenskiy, as the Trump administration renewed its push to end Russia's four-and-a-half year war in Ukraine.
They arrived following talks in Moscow, after which the Kremlin said it did not rule out the resumption of three-way negotiations also including the United States.
Both Moscow and Kyiv halted strikes on their capitals for three days to ensure the security of the US negotiators.
Ukrainian Foreign Minister Andrii Sybiha urged allies to ramp up pressure on Moscow, as well as to provide interceptors to down ballistic missiles, since Kyiv's stocks of these have run critically low.
Describing the attack as complex, aimed at causing "as much harm to life as possible", Zelenskiy said ballistic missiles were still "particularly difficult" to intercept.
Ukraine's air force said it downed nearly all cruise missiles and two ballistic missiles.
Prior to the talks, Russia had stepped up air attacks on Kyiv and nearby areas to nearly round-the-clock, rather than mainly at night, using faster jet-propelled drones that killed residents and disrupted activities.
Russia's defence ministry said Moscow hit military and logistic targets in Kyiv and the surrounding region, as well as in the Black Sea port of Chornomorsk, Russian news agencies said.
Aside from Kyiv, several other regions were targeted, Prime Minister Sergii Koretskyi said. Close to 100 people were evacuated after Russian drones hit a train in the northern Sumy region, he said.
The head of rail operator Ukrzaliznytsia said another commuter train was hit in the region. Passengers had been evacuated but some suffered shrapnel wounds, he said.
A rail worker was killed in a Russian double-tap drone strike on a passenger train in the southern city of Zaporizhzhia, emergency services said, adding that all passengers were evacuated.
Three people were hurt in an attack on a market on the outskirts of the Black Sea port of Odesa, the governor said.
Two people were killed and three injured in Kyiv region outside the capital, regional governor Tymur Tkachenko said.
Regional officials said two people were killed and nine injured near Nikopol, a frequent Russian target on the bank of the Dnipro River opposite the Russian-held Zaporizhzhia nuclear power station. One person died in southern Kherson region.
In Moldova, on Ukraine's western border, where Russian drones have regularly fallen, authorities said one drone had set fire to a field. A second had flown through Moldovan airspace for 17 minutes and then entered Romanian airspace.
In Kyiv, residents gathering near a heavily damaged apartment block said the let-up in attacks had allowed them to briefly forget the war.
"When foreign guests come to visit us, it's always quiet here. You kind of relax, exhale, feel calm ... It was so peaceful, as if there wasn't a war at all," supermarket worker Yana, 19, told Reuters.
"And then they left, and everything went back to normal. Russia gathers all its strength and, with more drones and ballistic missiles, starts bombing Kyiv again," she said.
As front lines remain largely static, both Russia and Ukraine have intensified long-range air strikes. Ukraine has targeted Russian oil facilities and warehouses of online retailers in an attempt to raise the cost to Moscow of continuing the war.
In Russia, Ukrainian drones damaged civilian infrastructure in the city of Saratov, while five people were killed in Ukrainian attacks on the Russia-annexed Crimea, as well as in the Bryansk and Kursk regions, local officials said.
