It said its armed forces "overnight launched a massive strike with high-precision long-range air, sea and ground-based weapons, as well as attack drones".
The attack came after Russian President Vladimir Putin warned US President Donald Trump he would respond to Ukraine's recent strikes on Russian airbases.
Russia's latest attack on Ukraine comes days after Kyiv launched its largest long-range drone strike on at least 40 Russian warplanes at four military bases.
Zelensky said 117 drones were used in the so-called Spider's Web operation by the SBU security service, striking "34% of [Russia's] strategic cruise missile carriers".
Authorities say Friday's attacks included 38 cruise missiles, which is the kind Ukraine targeted in Sunday's operation.
Zelensky said that three deaths had been confirmed in the strikes - all employees of Ukraine's state emergency services.
He said the attack used more than 400 drones and more than 40 missiles, and the number of people injured "may increase" in a post on X.
The Ukrainian leader added that "now is exactly the moment when America, Europe, and everyone around the world can stop this war together by pressuring Russia"
He also made a thinly veiled reference to Trump's apparent unwillingness to put pressure on Russia.
"If someone is not applying pressure and is giving the war more time to take lives – that is complicity and accountability," Zelensky wrote. "We must act decisively."