Louise was born in Güstrow in the family of Duke Gustav Adolph of Mecklenburg-Güstrow and Duchess Magdalena Sibylla of Holstein-Gottorp as a great-great-granddaughter of Frederick II of Denmark.

When it was deemed time for Frederick to marry and provide and heir to the throne, he was sent to a journey to Germany to choose a bride from some of the Protestant Princely houses.

When he reached Güstrow, he chose Louise because of her beauty, and his choice was wholeheartedly accepted as suitable from both the Danish royal house as well as from her family.

Initially, the marriage was described as happy; Louise reciprocated Frederick's attraction, and the French ambassador noted: "The crown princess loves her spouse intensely, and he lives with her in complete bliss".

Frederick even entered two morganatic marriages; in 1703, he committed bigamy with his mistress Elisabeth Helene von Vieregg, and in 1712 with Anna Sophie Reventlow.

The day after Queen Louise's funeral, Frederick IV married Anna Sophie Reventlow again, and less than two months later he had her crowned.