De Mist was born on 20 April 1749 in Voorburg near The Hague in the Netherlands. He went to school at Kampen, after which he studied law in Leyden from 1766 to 1768.
After graduation he became the junior secretary for the Kampen town, and later promoted to a position of a second secretary. At that time he was married to Arnelia Elisabeth Wilhlmina Strubberg, who died after giving birth to their tenth child, Julie Philippe Augusta de Mist. After the death of his wife de Mist married Elisabeth Margaretha Morre and he had no further children.
His career took on new heights in 1795 when the Republic of Batavia was created and he was appointed Governor-General. He was influential in the political life of Batavia, managing to calm conflict between a pro-French Batavian Party and the Federal Party over abolition of provincial autonomy. It was during his first year at the Cape that he founded Uitenhage.