Frances Environment Minister Nicolas Hulot, one of the most popular members of the government, announced his resignation on Tuesday in a major blow for President Emmanuel Macron.
"I am taking the decision to leave the government," Hulot said on France Inter radio in a surprise announcement, adding that he felt "all alone" on environmental issues within the government.
Hulot said he had not informed either Macron or Prime Minister Edouard Philippe of his decision.
"It's an honest and responsible decision," he added.
His departure is a major blow for 40-year-old centrist Macron, who is facing challenges on several fronts.
Due to slowing economic growth, his government is having difficulties drawing up the 2019 budget which saw Prime Minister Philippe announce at the weekend that he was dropping targets for reducing the deficit.
At the diplomatic level, Macron is struggling to convince his European partners of the need for a more integrated EU and his efforts to build a relationship with US President Donald Trump have yielded few concrete results.
Over the summer, he also suffered the first major political scandal of his 15-month term when his former bodyguard and senior security aide was filmed manhandling protesters while appearing to impersonate a policeman.
Hulot's announcement is likely to be received bitterly by Macron, who was starting a trip to Denmark to sell his EU agenda on Tuesday.
"The most basic of courtesies would have been to warn the president of the republic and the prime minister," government spokesman Benjamin Griveaux told the BFM news channel.
Hulot was formerly best-known as the presenter of the Ushuaia TV programme on French television.