His illegitimate son by Margaretha Catharina Bruyns (1595–1625), Frederick Nassau de Zuylestein was born in 1624 before his marriage and became the governor of the young William III of England for seven years.

On the death of Maurice in 1625 without legitimate issue, Frederick Henry succeeded him in his paternal dignities and estates, and also in the stadtholderates of the five provinces of Holland, Zeeland, Utrecht, Overijssel and Guelders, and in the important posts of captain and admiral-general of the Union (commander-in-chief of the Dutch States Army and of the Dutch navy).

For twenty-two years he remained at the head of government in the United Provinces, and in his time the power of the stadtholderate reached its highest point.

[2] It was marked by great military and naval triumphs, by worldwide maritime and commercial expansion, and by a wonderful outburst of activity in the domains of art and literature.

The chief military exploits of Frederick Henry were the sieges and captures of Grol in 1627, 's-Hertogenbosch in 1629, of Maastricht in 1632, of Breda in 1637, of Sas van Gent in 1644, and of Hulst in 1645.

During the greater part of his administration the alliance with France against Spain had been the pivot of Frederick Henry's foreign policy, but in his last years he sacrificed the French alliance for the sake of concluding a separate peace with Spain, by which the United Provinces obtained from that power all the advantages they had been seeking for eighty years.

The treaty of Munster, ending the long struggle between the Dutch and the Spaniards, was not actually signed until 30 January 1648, the illness and death of the stadtholder having caused a delay in the negotiations.

His widow commissioned an elaborate mausoleum in the Oranjezaal, a panoramic painted ballroom with scenes from his life and allegories of good government based on his achievements.