Born in Schwerin, she was the only daughter of Duke Louis of Mecklenburg-Schwerin, second son of Christian Louis II, Duke of Mecklenburg-Schwerin, and Princess Charlotte Sophie of Saxe-Coburg-Saalfeld.

Sophia Frederica, known as Sofie Frederikke af Mecklenburg-Schwerin in Denmark, was described as jolly, charming and intelligent.

[1] She had a hard time in the beginning adapting to her new, stiffer environment, but became quite popular.

[2] During the first ten years of her marriage (1774-1784), she gave birth to three daughters, the eldest two were stillborn and the third lived only five months;[3][4] it was only in 1786 when she had the first of her living children, the future King Christian VIII.

The harmonious friendship between the spouses created a fear that Sophia Frederica's influence over her husband would lead to her interfering in politics.