The overnight attack killed two people and wounded three others.
The latest drone attack came as Russia has intensified aerial strikes on the capital this month, and warned the West against escalating the conflict after the United States agreed to greenlight F-16 deliveries.
Ukraine said the latest attack in Kyiv was "the most important" of the invasion, with more than forty out of 54 drones targeting the capital.
"Every time you shoot down enemy drones and missiles, lives are saved... you are heroes!" Zelensky told his air defence forces on Sunday morning, also thanking rescuers.
This was the 14th drone attack on the Ukrainian capital by Russia this month.
"People are in shock. There's a lot of damage, the windows were broken, the roof was damaged," said Sergei Movchan, a 50-year-old resident whose house was damaged by debris.
Kyiv had been relatively spared since the beginning of the year, but in May its residents have had to live with almost nightly air raid sirens and thundering explosions.
"Russians are intimidating us. But I think it's the agony of their regime," Movchan said.
- Kyiv a 'symbol' -
In Kyiv the air raid alert lasted more than five hours as the attack was carried out in several waves.
Kyiv's mayor, Vitali Klitschko described the assault as "massive" with drones "arriving from several directions at once".
The Kyiv military administration said that "more than 40 Russian drones were destroyed by air defence" systems in the "most important drone attack against the capital since the start of the invasion" in February 2022.
Authorities reported that two killed and three others wounded as debris of the downed drones fell in several districts.
Sunday was to be celebrated as Kyiv's city day, usually marked by street concerts and celebrations.
"Today the enemy decided to 'congratulate' the population on Kyiv Day with the help of their killer drones," the authorities said.
Congratulating residents on Kyiv Day, presidential chief of staff Andriy Yermak said the capital had "stood up" to Russia.
"Kyiv, a city of free and brave people, has become a symbol of Ukraine's unbreakable spirit and the Kremlin's failed imperial ambitions," Defence Minister Oleksiy Reznikov said.
Ukraine's air force said that "a record" of 54 drones were launched from the regions of Briansk and Krasnodar in Russia, adding that 52 were destroyed.
It said Russia used Shahed drones from Iran, and presidential aide Mykhaylo Podolyak to vow new sanctions against Iran.
- 'Key ally' -
"Tehran has become a key ally of Moscow in this war, deliberately supplying it with weapons for attacks on civilian cities," Podolyak said.
This week Zelensky had blasted Tehran's "support for evil" and appealed to the Iranian people.
Iran had answered by saying Zelensky's accusation was an attempt to gain the West's military and financial support.
After Kyiv long asked for advanced warplanes, the United States on Friday said it would allow Kyiv to acquire F-16 fighter jets, the most sophisticated material yet supplied by the West.
Foreign Minister Sergei Lavrov on Sunday said Western nations were "playing with fire" by agreeing to supply Ukraine with F-16.
Lavrov called the move an "an unacceptable escalation" of the conflict, in a TV interview posted on social media.
As the drone war rages, Russia has blamed Ukraine -- and its Western backers -- for increasing artillery and drone attacks on its territory, accusations Kyiv has mostly denied.
Most drones target Russian regions bordering Ukraine but they have sometimes reached hundreds of kilometres inside Russia, including a thwarted attack on the Kremlin itself.
The past week also saw an unprecedented two-day incursion from Ukraine claimed by two anti-Kremlin groups, with Russia using its air force and artillery to push back the fighters.
The reports of attacks come at a time when Kyiv says it is finalising plans for a counter-offensive to recover lost territory, including the Crimea peninsula which was annexed in 2014.
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