His half-brother succeeded Charles's father as Adolphus Frederick III, Duke of Mecklenburg-Strelitz.
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Charles was married on 5 February 1735 in Eisfeld to Princess Elizabeth Albertine of Saxe-Hildburghausen, daughter of Ernest Frederick I, Duke of Saxe-Hildburghausen.
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Charles was born in Strelitz, the only son of the reigning Duke of Mecklenburg-Strelitz, Adolphus Frederick II, and his third wife, Princess Christiane Emilie of Schwarzburg-Sondershausen.
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Duke Adolf Friedrich IV of Mecklenburg (5 May 1738 – 2 June 1794); succeeded his half-uncle as reigning duke with the style Ducal Serene Highness.
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Father of Louise of Mecklenburg-Strelitz; succeeded his older brother as reigning duke with the style Ducal Serene Highness, until 28 June 1815, when Mecklenburg-Strelitz was elevated to grand ducal status, at which time Duke Charles II became Grand Duke Charles II.
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He was born in Mirow to Charles Louis Frederick of Mecklenburg and his wife Princess Elizabeth Albertine of Saxe-Hildburghausen.
Duke Charles Louis Frederick of Mecklenburg was born in Mirow the second son of Duke Charles Louis Frederick of Mecklenburg, Prince of Mirow, and his wife Princess Elizabeth Albertine of Saxe-Hildburghausen.