When Maurice of Nassau died, he made his half-brother Frederick Henry promise to wed. Frederick married Amalia on 4 April 1625. Their marriage produced five children who lived to adulthood, and four who died young. Their oldest, stadtholder William II (1626-1650), married Mary, The UK Princess Royal. When Frederick Henry became stadtholder after the death of his half-brother Prince Maurice, his influence grew substantially, as did Amalia's. Together Frederick Henry and Amalia succeeded in expanding court-life in The Hague. They had a number of palaces built, including Huis ten Bosch. Amalia was the prime mover of a number of royal marriages, including that of her son William II to Mary, Princess Royal of England and Scotland (daughter of King Charles I of England) and of their daughters with a number of German princes. After the death of her son William II she became the main guardian of her grandson William III (Prince William III of Orange and later also King William III of England).

Henrietta Maria took an immediate dislike to George Villiers, 1st Duke of Buckingham, the King's favourite. However, after Buckingham'd death in August 1628, her relationship with the her husaband, Charles I, improved and they finally forged deep bonds of love and affection. Her refusal to give up her Catholic faith alienated her from many of the people and certain powerful courtiers such as William Laud, Archbishop of Canterbury and Thomas Wentworth, Earl of Strafford. Charles, on the other hand, had definite leanings towards Catholicism, and, once he had reached maturity, did not share his father's sexual ambivalence.