His mother, the Dowager Princess Gisela Agnes, acted as regent on his behalf, but King Frederick I of Prussia, according to the late Prince's will, became his "upper guardian".

From the beginning of the regency, conflicts arose between the king and the dowager princess: Frederick preferred a Reformed (Calvinistic) education for Leopold, but Gisela Agnes, a devout Lutheran, planned to raise her son in her own faith.

[citation needed] In the meanwhile, the king had founded the Knight's Academy (German: Ritterakademie) in Brandenburg an der Havel, and in 1708 decided to send Leopold there for his education.

After Leopold's return in 1711, King Frederick I wanted to make him a commander in the Prussian army, but the opposition of the dowager princess led him to withdraw this idea.

[citation needed] Instead, Leopold traveled again, this time to England, where he attended the opera in London and visited the University of Oxford, whose famous library specially interested him.

As of 1702, the rule of primogeniture was instituted in Anhalt-Köthen; for this reason, Leopold forced his younger brother Augustus Louis to resign his joint rulership.

As compensation, Leopold gave him the estate of Güsten, with its old Schloss built in 1547 by Prince George III, and the town of Warmsdorf with all its revenues, in addition to other concessions.

Leopold most likely made Bach's acquaintance at the wedding of his sister Eleonore Wilhelmine to Ernest Augustus I, Duke of Saxe-Weimar, which was held at his mother's estate in Nienburg on 24 January 1716.

Bach was not able to break easily from his former employer Duke William Ernest of Saxe-Weimar, who imprisoned him from 6 November-2 December 1717 for not following correct procedures in requesting release from his post as Konzertmeister at the court of Weimar.

[citation needed] In Weimar on 27 June 1725 Leopold married for a second time to Charlotte Frederike (b. Siegen, 30 November 1702 – d. Stadthagen, 22 July 1785), daughter of Frederick William Adolf, Prince of Nassau-Siegen.

They had two children: The only son and heir of Leopold succumbed to smallpox in August 1728, and the prince's second daughter, who also contracted the disease, died in early September.