PARIS — President Emmanuel Macron’s most senior government ally forced his boss to accept his resignation on Wednesday, a humiliation for the embattled French leader who is already struggling with sinking popularity and weakened authority.

Mr. Macron has had a difficult start to the fall political season, and it became even more so this week. Gérard Collomb, the 71-year-old interior minister whose balding head stood out among Mr. Macron’s more youthful cadre, had announced that he wanted to depart the government weeks ago.

The two men have been increasingly at odds — Mr. Collomb criticized the president’s “lack of humility” in a recent interview. Those differences extended even to which one of them would get to decide the timing of the interior minister’s departure. Mr. Collomb offered his resignation on Monday, but Mr. Macron refused to accept it, finally giving the green light for the departure only on Wednesday, after an unusual public standoff.

Trying to dampen reports that Mr. Collomb’s departure would throw the presidency into further disarray, Benjamin Griveaux, a government spokesman, said, “Nothing that has happened in the past 48 hours is akin to a political crisis.”