Louise was betrothed to Frederick, Prince Regent of Baden in 1854, and they married 20 September 1856 at Neues Palais in Potsdam. Frederick had been regent because of his brother Louis's insanity, and was proclaimed Grand Duke of Baden when doctors declared that there was no chance of recovery. As the only daughter of the Prussian crown prince (and later emperor), their marriage caused Baden to gain a great deal of importance, and even more so once the German Empire was founded.
Within a few weeks of their marriage, the new grand duchess was already pregnant with their first child, Hereditary Grand Duke Frederick. Louise was a happy wife and mother, writing to a friend that "since we last met, my life has become so much more beautiful, more precious, to me, my happiness is so much richer and deeper than before".
Louise and Frederick disliked the stiffness of the Karlsruhe court, and gladly escaped to their castle on the island of Mainau. They were popular in Baden, and everyone spoke with affectionate pride of their grand duke and duchess in Constance, where the couple had a summer residence.