He was born in Paris, the son of Auguste Casimir-Perier, the grandson of Casimir Pierre Perier, premier of Louis Philippe, and the great grandson of Claude Périer, one of the founders of the Bank of France. He entered public life as secretary to his father, who was Minister of the Interior under the presidency of Thiers.
In 1874 he was elected General Councillor of the Aube département, and was sent by the same département to the Chamber of Deputies in the general elections of 1876, and he was always re-elected until his presidency. In spite of the traditions of his family, Casimir-Perier joined the group of Republicans on the Left, and was one of the 363 on the Seize-Mai (1877). He refused to vote the "expulsion of the Princes" in 1883, and resigned as Deputy upon the enactment of the law (26 June 1886) because of his personal connections with the family of Orléans.
On 17 August 1883 he became Under-Secretary of State for War, a post he retained until 7 January 1885. From 1890 to 1892 he was Vice President of the Chamber, then in 1893 President. On 3 December he became President of the council, holding the department of Foreign Affairs, resigned in May 1894, and was re-elected President of the Chamber.
On 24 June 1894, after the assassination of President Carnot, he was elected President of the Republic by 451 votes against 195 for Henri Brisson and 97 for Charles Dupuy. His presidency lasted only six months. The resignation of the Dupuy ministry on 14 January 1895 was followed the next day by that of the President. Casimir-Perier explained his action by the fact that he found himself ignored by the ministers, who did not consult him before taking decisions, and did not keep him informed upon political events, especially in foreign affairs.
As of 2019, of all Presidents of France through its history, Casimir-Perier had the shortest presidency.
From that time he completely abandoned politics, and devoted himself to business – especially mining. At the trial of Alfred Dreyfus at Rennes, Casimir-Perier's evidence, as opposed to that of General Mercier, was of great value to the cause of Dreyfus.