After weeks of talk of a looming government shake-up, he said MPs would review resignation requests from Strategic Industries Minister Oleksandr Kamyshin, Justice Minister Denys Maliuska and Environment Minister Ruslan Strilets.
"I will continue working in the defence sector but in a different role," Kamyshin wrote on the Telegram messaging app, confirming his exit.
Kamyshin, 40, was appointed in March 2023 and has spearheaded Ukraine's effort to ramp up defence production of everything from attack drones to long-range missiles as the country's forces battle Russia, a much better-armed and larger foe.
In the year after the Kremlin's full-scale invasion in February 2022, he carved out an image as an effective wartime manager running Ukraine's railways, a vital logistics artery for both civilians and the military.
MPs and political analysts have expected major changes in the government since summer began.
The exit of the three ministers adds to the uncertainty around the government with at least five other ministerial portfolios vacant after sackings earlier this year.
President Volodymyr Zelenskiy and his political team could move to fill all the positions now in a bid to bring in order before he travels to the United States this month to attend the United Nations General Assembly.
The Ukrainian leader said last week that he hoped to have a meeting with US President Joe Biden and his two possible successors to present a "victory plan" that would coerce Russia into ending its war in Ukraine.
I received preliminary reports on the Russian strike in Poltava. According to available information, two ballistic missiles hit the area. They targeted an educational institution and a nearby hospital, partially destroying one of the telecommunications institute's buildings.… — Volodymyr Zelenskyy / Володимир Зеленський (@ZelenskyyUa) pic.twitter.com/TNppPr1OwFSeptember 3, 2024
Ukraine's first lady said on Tuesday at least 47 people were killed and 206 wounded when Russia struck a military institute in the central town of Poltava with two missiles.
Photographs posted on social media showed several bodies lying on the ground covered in dust and debris, with the badly damaged side of a large building behind them.
Reuters could not immediately verify the images.
"The Russian scum will definitely be held accountable for this strike," Zelenskiy said on the Telegram messaging app.
He ordered a full and prompt investigation, saying the strike with two ballistic missiles damaged a building of the Military Institute of Communications.
It was not immediately clear who the victims were.
Ukrainian military bloggers suggested some might be cadets or recently mobilised men undergoing training.
The use of ballistic missiles - which hit targets hundreds of kilometres away within a few minutes of their launch - meant the victims had almost no time to find cover after the air raid siren sounded, the foreign ministry said.
"This is a stunning tragedy for all of Ukraine. The enemy hit an educational institution and a hospital," Ukraine's first lady Olena Zelenska wrote on X.
Some Ukrainians left worried messages on the institute's Facebook page seeking information about their loved ones.
"One of the institute's buildings was partially destroyed, and many people were trapped under the rubble," the defence ministry said on Telegram.
"Thanks to the co-ordinated work of rescuers and medics, 25 people were rescued, 11 of whom were taken from the rubble. The rescuers are currently continuing their work."
Russia did not immediately comment on the attack.
In Poltava, 300km southeast of Kyiv and 120km to the nearest Russian border, governor Filip Pronin said that many residents had donated blood for the wounded.
Local authorities announced three days of mourning.
Serhiy Beskrestnov, a prominent Ukrainian Telegram blogger followed by many radio, communications and electronic warfare specialists in Ukraine's military, posted a tribute to "my signals operator comrades".
Fighting has intensified over the past month, with Russian forces advancing in heavy battles in eastern Ukraine while Ukrainian troops have mounted their first large-scale cross-border assault into a Russian region, for which Russia has vowed to retaliate.
