Ernest Frederick succeeded his father as Duke of Saxe-Hildburghausen when he was only eighteen years old in 1745; as a result his mother, the Dowager Duchess Caroline, acted as a regent on his behalf until he reached adulthood, in 1748.

He donated a library to the city, but finally his excessive prodigality in exaggerated court pomp and military splendor drew the attention of the highest places to the financial situation of his country.

Finally, the huge fire of the city of Hildburghausen in 1779, forced Ernst Frederick to move to his hunting residence in Seidingstadt, where he died a year later.

In the Hirschholm Palace, north of Copenhagen on 1 October 1749, Ernst Frederick was first married to Princess Louise of Denmark, daughter of the King Christian VI.

They had one daughter: In the Christiansborg Palace, Copenhagen on 20 January 1757, five months after the death of his first wife, Ernst Frederick was married for the second time to Christiane Sophie Charlotte of Brandenburg-Bayreuth.