Brought up with relatives at the Danish court, he spent most of his life in Denmark, serving as royal governor of the twin duchies of Schleswig-Holstein from 1769 to 1836 and commander-in-chief of the Norwegian army from 1772 to 1814.

His mother was a daughter of King George II of Great Britain and Princess Caroline of Ansbach and a sister of Queen Louise of Denmark.

After his cousin, King Christian VII, acceded to the throne in 1766, he was appointed lieutenant general, commander of the Royal Guard, knight of the Order of the Elephant and member of the Privy Council.

[3] Shortly after, Charles fell into disfavour at court, and in early 1767 he and Louise left Copenhagen to live with his mother in the county of Hanau.

In 1769, Prince Charles of Hesse was appointed royal Governor of the twin duchies of Schleswig and Holstein (initially only the royal share, so-called Holstein-Glückstadt before in 1773 the king also acquired the ducal share in Holstein) on behalf of the government of his brother-in-law, King Christian VII of Denmark and Norway.

[4] During the War of the Bavarian Succession in 1778–79, he acted as a volunteer in the army of Frederick the Great and gained the trust of the Prussian king.

In response to an inquiry from the king, Charles said, "Sire, I am not more sure of having the honour of seeing you, than I am that Jesus Christ existed and died for us as our Saviour on the cross."

Prince Charles was put in command of a Norwegian army which briefly invaded Sweden through Bohuslän and won the Battle of Kvistrum Bridge.

The army was closing in on Gothenburg, when peace was signed on 9 July 1789 following the diplomatic intervention of Great Britain and Prussia, bringing this so-called Lingonberry War to an end.

During the retreat, the Danish-Norwegian army lost 1,500–3,000 men to hunger, disease, poor sanitary conditions, and exposure to continual autumn rainfall.

Following the death of his father's first cousin, prince Friedrich Wilhelm von Hessenstein, he inherited the estate of Panker in Holstein in 1808.