Upon the death of his uncle in 1504 Henry inherited the Nassau possessions in the Netherlands, including the wealthy lordship of Breda in the duchy of Brabant.

He was Captain General in the war with Guelders between 1511 and 1513, and fought with Maximilian of Austria against France until 1514, participating in the battle of Guinegate (1513).

Although Henry, who attended the Diet of Augsburg in 1530, was at first not averse to Martin Luther and his teachings, he later followed Charles' example and remained a staunch Catholic.

For example, he commissioned Italian architect Tomasso Vincidor da Bologna to completely rebuild his castle at Breda in a renaissance style in 1536, one of the first of such buildings north of the Alps.

His third marriage to Mencia de Mendoza y Fonseca was mainly encouraged by Charles V, as part of his plan to make the nobility of Spain and the Low Countries mix.

Henry lies buried beneath the grave monument he had erected for his uncle Engelbert in the Grote kerk at Breda.