He was the second son of Frederick, Duke of Mecklenburg-Grabow (1638–1688), and his wife, Landgravine Christine Wilhelmine of Hesse-Homburg (1653–1722).

Mecklenburg-Schwerin began its existence during a series of constitutional struggles between the duke and the nobles.

The heavy debt incurred by Karl Leopold, who had joined Russian Empire in a war against Sweden, brought matters to a head; Charles VI interfered, and in 1728 the Imperial Aulic Council[1] declared the duke incapable of governing.

His brother, Christian Ludwig II, was appointed administrator of the duchy.

There was one daughter born of this marriage, the Grand Duchess Anna Leopoldovna of Russia.