On 1 October 1791, she married her cousin William of the Netherlands, son of StadtholderWilliam V, Prince of Orange, in Berlin. The marriage was arranged as a part of an alliance between the House of Orange and Prussia, but it was also, in fact, a love match and became very happy. The young couple went to live at Noordeinde Palace in The Hague. In 1795, the French invaded the Dutch Republic, and the princely family went into exile. They first stayed in England, and from 1796 in Berlin. In 1806, Wilhelmine was again forced to flee from the French army, and settled under difficult economic circumstances in Poland. The princess returned to The Hague in the beginning of 1814.
Princess Wilhelmine became Queen of the Netherlands in 1815. At the time, the Netherlands included the present-day country of Belgium. Queen Wilhelmine was modest and stayed in the background, and she did not play any dominant role as queen. She was not a popular queen, and was criticised for isolating the royal family; in the area of modern Belgium, she was criticised for her German style of dressing. She was interested in painting, attended exhibitions, and helped to protect museums and support artists. She was herself a student of art and regarded as a talented dilettante, ultimately being inducted as an honorary member to the Royal Academy of Fine Arts.
Beginning in 1820, her health worsened, and after 1829, she was rarely seen in public. She died at Noordeinde Palace in The Hague in 1837, aged 62, and is entombed in the New Church in Delft.