He succeeded his grandfather as Margrave of Baden-Durlach in 1738 and ruled personally from 1746 until 1771, when he inherited Baden-Baden from the Catholic line of his family.

He was regarded as a good example of an enlightened despot, supporting schools, universities, jurisprudence, the civil service, the economy, culture, and urban development.

Together with his architect, Friedrich Weinbrenner, Charles Frederick was responsible for the construction of the handsome suite of classical buildings that distinguish Karlsruhe.

They had five children: Charles Frederick married Louise Caroline, Baroness Geyer of Geyersberg as his second wife on 24 November 1787.

Their succession rights were reinforced when Baden was granted a constitution in 1818, and recognised by Bavaria and the Great Powers in the Treaty of Frankfurt, 1819.