In 2016, Cazeneuve was appointed prime minister by President François Hollande, after Manuel Valls resigned to concentrate on his candidacy for the 2017 presidential election.

Following the election of Emmanuel Macron as President of the French Republic, Cazeneuve resigned from office and returned to private practice.

During the 2024 French political crisis, Cazeneueve was reported to be the front-runner candidate for Prime Minister but was ultimately passed over in favor of Michel Barnier.

During his studies at the Institut d'études politiques de Bordeaux,[4] he led the Young Radicals of the Left movement in the Gironde department.

In 2007, Cazeneuve represented the Socialist Party in the legislative election for the 5th Constituency of Manche, defeating UMP candidate Jean Lemière with 58.96% of the vote.

In his second term as mayor, he campaigned to promote the maritime character of the city, organising a nautical festival that featured an international sailing competition.

Cazeneuve was elected to head the new commune of Cherbourg-Octeville in 2001,[4] succeeding Jean-Pierre Godefroy and defeating the Rally for the Republic (RPR) candidate Jean Lemière.

In the 2012 legislative elections he was re-elected to the National Assembly in the newly redrawn 4th Constituency of Manche, with Geneviève Gosselin, the deputy mayor of Cherbourg-Octeville, as his alternate.

He won the election in June with 55.39% of the vote, but had to resign to assume his post in the new government, leading to Gosselin becoming the new deputy to the National Assembly.

During a vote on a counter-terrorism law, he proposed an amendment that would give authority to demand that search engines de-list certain website without the approval of a judge.

In July 2015, he proposed a reform to the rights of foreigners in France, which would fundamentally change policies concerning entry and length of stay.

"[7] Reports after that meeting indicated that all EU citizens entering or leaving the free-travel area, known as Schengen, should undergo "systematic" screening against pan-European databases.

This would be on a temporary basis until the European commission modified the Schengen rules to make the new borders regime mandatory and obligatory; that could take months to enact.

[9][10] The appointment was considered difficult, since it resulted in a change of leadership in the Interior Ministry at a time when the French terror alert was at its highest level.

[citation needed] In 2022, Cazeneuve resigned from the Honorary Board of Fight Impunity, a Brussels-based human rights NGO, following corruption allegations against its founder, Antonio Panzeri.

On 12 November 2023, he took part in the March for the Republic and Against Antisemitism in Paris in response to the rise of anti-Semitism in France since the start of the Israel–Hamas war.

[16] Following the 2024 French legislative election, France experienced months of political deadlock, during which President Emanuel Macron considered various candidates for the position of Prime Minister.

[17][18] His candidacy sparked controversy with the NFP, with members of La France Insoumise (LFI) condemning it as a "total betrayal of millions of voters".