A majority of 272 MPs voted to dismiss Deputy Prime Minister Oleksandr Kubrakov, who oversaw the reconstruction program and championed efforts to set up a Black Sea shipping lane during a de-facto Russian blockade.
The exit of the 41-year-old comes amid plans to break up his powerful ministry into two separate portfolios, MPs said.
"We expect the government will make a decision to separate the ministries. Then later in the second half of May, the new appointments will be made," Yevhenia Kravchuk, an MP from the ruling Servants of the People party said.
Kubrakov said on Facebook that his dismissal had not been discussed with him in advance and that he had not been given a chance to defend his tenure in a presentation to parliament.
MPs also accepted the resignation of Agriculture Minister Mykola Solsky who is being investigated for alleged involvement in an illegal acquisition of state-owned land.
The 44-year-old denies the allegations.
The government now has five vacant ministerial positions, said Oleksiy Honcharenko, an MP from the opposition European Solidarity party.
There are more than 20 ministerial portfolios in the current government.
Officials have repeatedly said they plan to reform the government's structure and cut the number of ministries as the country faces a huge budget deficit with most state revenues allocated towards defence efforts.
Iryna Friz, a European Solidarity party MP, criticised any suggestion of increasing the number of ministries.
"This chaotic activity will hurt the efficiency of the ministries," she said.
"This chaotic approach is not right and is damaging especially as we are now in a wartime period."
Kubrakov's giant ministry was set up in December 2022.
As Zelenskiy approaches the end of his five-year term this month and with no elections scheduled because of the war, some politicians have called on him to form a government of national unity instead.
Ukrainian President Volodymyr Zelenskiy said on Thursday that Ukraine could stop Russian forces advancing in the east if allied countries increased the supply of arms.
I welcomed — Volodymyr Zelenskyy / Володимир Зеленський (@ZelenskyyUa) @EP_President Roberta Metsola today, on Europe Day, which celebrates a peaceful and united Europe. We are working together to strengthen our position in protecting life for Ukraine, our region, and Europe as a whole. Now, seventy-nine years after Nazism was… pic.twitter.com/Ko7pqSSzGzMay 9, 2024
Russia has been making small but steady territorial gains in the east of the country since the start of the year, with Ukraine's forces depleted and weapons and ammunition running perilously low.
"We are putting maximum pressure on our partners to increase weapon deliveries," Zelenskiy said at an open air briefing in the centre of the capital.
"If the delivery of weapons is increased, we will be able to stop (Russian forces) in the east, where they have the initiative."
As he spoke, air raid sirens started to blare, a reminder of the threat of Russian missile and drone attacks which have intensified across the country, causing power outages for hundreds of thousands of civilians.
"This is their true attitude to peace," Zelenskiy said in reference to Russia as officials began moving towards a shelter.
Metsola was in Kyiv on Europe Day, which celebrates peace and unity across the continent.
"How are you feeling Roberta?" he asked, turning to Metsola who was standing a few metres away.
"I am alright but, as you say, it's Europe Day. Look at this, now I get an idea of what you live through every day," she replied.
Ukrainian troops withdrew from three eastern villages in late April, and Ukraine's top commander has said the situation at the front had worsened.
The U.S. decision to approve a huge military aid bill last month was welcomed by Kyiv, but many units have yet to receive new arms and warn that time is running out.
Zelenskiy acknowledged Ukraine's need for more troops, saying that the lack of forces was creating a "difficult situation" near Avdiivka, a town Russia has captured, and Pokrovsk, which is still in Ukrainian hands.
Additional brigades need to be equipped as they arrive to hold back Russian forces, Zelenskiy said, making aid that is "weeks and months away" more pressing.
"Deliveries are taking place but not in the amounts that were ... voted for," he said.
Zelenskiy added that increased domestic production of drones and artillery shells had helped Ukraine in its battle against Russia's continued onslaughts.
