Frederick was born at Schwerin, the son of Christian Ludwig II, Duke of Mecklenburg, and his wife, Duchess Gustave Caroline of Mecklenburg-Strelitz.

In his childhood and youth his great-aunt Duchess Augusta of Mecklenburg-Güstrow had great influence on the intellectual and spiritual development of Frederick, essentially in instilling the beliefs of Pietism.

He encouraged the school system, promoted the textile manufacturing and abolished torture.

Frederick married on 2 March 1746 at Schwedt to Duchess Louise Frederica of Württemberg, daughter of Frederick Louis, Hereditary Prince of Württemberg, and his wife Margravine Henrietta Maria of Brandenburg-Schwedt.

At his death, the dukedom was inherited by his nephew Frederick Francis, a son of his brother Louis.