Henry Casimir II of Nassau-Dietz was the eldest son of Willem Frederik of Nassau-Dietz and Albertine Agnes of Nassau, daughter of Frederick Henry, Prince of Orange, stadtholder of Holland, Zeeland, Utrecht, Guelders, and Overijssel.
When his father, a member of the branch of Nassau-Dietz, died in 1664, he was made stadtholder of Friesland and Groningen (under guardianship of his mother as he was then seven years old). In 1675, Friesland voted to make its stadtholdership hereditary in the house of Nassau-Dietz. Hendrik Casimir II was therefore the first Friesian stadtholder. In 1683, he married his cousin Henriëtte Amalia of Anhalt-Dessau, daughter of John George II, Prince of Anhalt-Dessau. Hendrik Casimir was succeeded as stadtholder by his son Johan Willem Friso of Orange-Nassau.