In 1786 he joined the Prussian Army, where he obtained the rank of Major General. From 1792 to 1794, he fought in military campaigns on the Rhine.
After the death of his father and his mentally disabled older brother's renunciation of succession rights (1797), Frederick Ferdinand inherited the non-sovereign Prussian state country of Pless, but in 1803 he returned to the Prussian army.
After the Battle of Jena, he commanded his own regiment at Zehdenick near the enemy lines, but was forced to withdraw to Bohemia in order to ensure the disarmament of the Austrians. Soon afterwards he retired from the military and made a trip to the Netherlands and France before his return to Pless. During the War of the Sixth Coalition in 1813, he was Commander of the Silesian countryside.
When the young Duke Louis Augustus died without direct heirs in 1818, Frederick Ferdinand, as his closest male relative, succeeded him in the sovereign duchy. Shortly after, he ceded Pless to his brother Henry.
During a trip to Paris in 1825, Frederick Ferdinand and his wife converted to Catholicism. His attempts to convert Köthen to the Catholic faith encountered stiff resistance. The duke chose as confessor the Belgian Jesuit Peter Jan Beckx.
In Grimschleben near Nienburg he brought in the classicist architect Gottfried Bandhauer to realize some remodeling of his palace. By 1828 he founded a colony in southern Ukraine called "Askania-Nova" (New Ascania), located in the steppes of Tauri, in the northern peninsula of Crimea.
Under his government, Bandhauer also built (between 1823 and 1828) the Ferdinandsbau in Schloss Köthen, the monastery and hospital of the Brothers of Mercy (German: Barmherzigen Brüder) in 1829, and the Catholic Church of St. Mary (Kirche St. Maria) in 1830, in the crypt of which Frederick Ferdinand was buried shortly thereafter.
On his death without issue in 1830, Frederick Ferdinand was succeeded by his brother Henry.