In 1515, Casimir and his younger brother George deposed their father, who had greatly burdened the finances of the margraviate with his lavish lifestyle.

When Elector Joachim I of Brandenburg visited Kulmbach during his journey to Augsburg, and wanted to plead for the release of Casimir's father, he was denied access to Plassenburg Castle.

The Elector's brother, Albert of Brandenburg, then turned against him and sided with Emperor Charles V, and was rewarded with a cardinal's hat.

At that point, his brother George took up the regency of Brandenburg-Kulmbach until Casimir's eldest son, Albert II Alcibiades, came of age in 1541.

Casimir was a vassal of Emperor Maximilian I and fought in 1499 alongside his father and Margrave Christopher I of Baden as the commander of the Swabian League against the Old Swiss Confederacy and led the negotiations that resulted in the Peace of Basel.

In 1513, he was imperial commissioner at the assembly of the Swabian League at Nördlingen dealing with a breach of the peace by Götz von Berlichingen.

[1] Among the traditional arguments of the Burgraves and Margraves with the Imperial City of Nuremberg was a dispute in 1502 over the protection of the fair in Affalterbach.

The Nuremberg had to retreat from Affalterbach with heavy losses and surrender their banners, which were put on display in the church in Schwabach.

In the spring of 1525 Casimir and the neighboring princes met in Neustadt an der Aisch to discuss a common response to the riots that threatened to spill over from Swabia into the Odenwald.

In Kitzingen, he wanted to set an example: he promised the bailiff Louis von Hutten that the lives of the residents would be spared.

Contemporary reports claim that the market squares of Rothenburg and Schweinfurt were dyed red by the blood of the beheaded rebels.

At the coronation of the future German Emperor Ferdinand I as King of Bohemia in 1527, Casimir, who was seriously marked by disease, joined a military campaign in Hungary against John Zápolya.

Because his brother George the Pious also joined, Casimir returned to appoint a stadtholder for their Franconian possessions and to raise additional troops.

On 27 September 1527, he died of dysentery in Buda, in the presence of his brother George and King Ferdinand, to whom he entrusted the care of his five-year-old son Albert II Alcibiades.

Theodore Hirsch concludes his biography with the statement that because of the atrocities Casimir committed, so far no biographer had written a balanced description of his life.