A majority of 272 lawmakers voted to dismiss Deputy Prime Minister Oleksandr Kubrakov, who oversaw the reconstruction programme 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, lawmakers said.
Kubrakov said on Facebook that his dismissal had not been discussed with him in advance of the vote and that he had not been given a chance to defend his tenure in a presentation to parliament.
Parliament 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.
It was not immediately clear who would replace the two ministers. Yaroslav Zhelezniak, a senior lawmaker, said Kubrakov would not be reappointed.
The government now has five vacant ministerial positions, said Oleksiy Honcharenko, a lawmaker from the opposition European Solidarity party.
There are over 20 ministerial portfolios in the current government.
Ukrainian 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.
As Zelenskiy approaches the end of his five-year term this month and with no elections scheduled because of the war, some Ukrainian politicians have called on him to form a government of national unity instead.
