French Foreign Minister Laurent Fabius said on Wednesday that he would leave the government ahead of a wider reshuffle before he took up a new post as head of the constitutional court.
The reshuffle is an opportunity for President Hollande to deal with the low approval ratings and increasing dissatisfaction in his governing party.
Fabius, 69, who played an active role in plugging an international agreement with Iran restricting its nuclear programme, he also pushed for a global climate change deal.
President Hollande has named Laurent Fabius head of the French Constitutional Court.
The reshuffle will take place later this week.
This is also a critical time for Hollande, who is considering to revoke French citizenship from people sentenced for terrorism, the bill is far from certain to be admitted in spite of passing the first obstacle in parliament on Tuesday.