Louise of Mecklenburg-Güstrow was the daughter of Duke Gustav Adolf of Mecklenburg-Güstrow and Magdalene Sibylle, born Princess of Schleswig-Holstein-Gottorp. She was born in the small North German Duchy as the seventh of eleven children – nine girls and two boys. Louise's childhood and adolescence were strongly influenced by pietism and the limited finances of the duchy.

Louise soon discovered that her marriage to Frederik IV was not a bed of roses. The life together was marred by Frederik IV’s extramarital affairs, which caused Queen Louise much pain and led to embarrassing scenes at the court. Frederik IV even entered into two morganatic marriages with his mistresses while he was still married to Louise. That was bigamy, which was strictly forbidden, but as Denmark’s absolute king, he was above the law.

While surrounded by the pomp and splendour of the absolute monarchy, Louise led a retired life. Unlike her husband, she was never popular with the Danish public. She never courted popularity either but kept to herself, seeking salvation through her pietist beliefs and personal piety.  She also dedicated herself to new endeavours on her estates. Among other undertakings, Louise founded the Donse Krudtværk, one of the earliest gunpowder plants in North Zealand. She also established a large brickworks in the town of Nivå. 

Queen Louise died on 15 march 1721 and was entombed in Roskilde Cathedral on 4 April that same year. The day after the funeral, her widowed husband, Frederik IV, married Anna Sophie Reventlow, his long-standing mistress and morganatic wife. Now she became his lawful wife, and soon after, she was also crowned Queen of Denmark-Norway.

Queen Louise was the last queen to spend the night at Rosenborg Castle. However, she only had a few stays there, as the castle fell out of use as a royal residence during her time as queen. Rosenborg Castle had become outdated. In 1699, construction began on a new summer residence, Frederiksberg Castle, which was ready for use in 1703.