Im Zentrum der Historienserie stehen die teils romantischen, teils dramatischen Abenteuer der schottischen Monarchin Mary, Queen of Scots - in Deutschland unter dem Namen Maria Stuart populär. Bereits als Säugling wurde sie 1543 nach dem Tod ihres Vaters zur offiziellen Thronfolgerin, jedoch übernahm ihre Mutter die Regentschaft.

Reign begins its third season with Mary and Francis realizing that they are more powerful together than apart, believing there is hope for them to move forward, leaving behind the anger and hurt. It also introduces us to another Court, that of Elizabeth, "Virgin" Queen of England. Still early in her reign, Elizabeth faces opposition on all sides, particularly from men who doubt a woman's ability to rule. Like Mary, and Catherine de Medici, she struggles to hold onto power, and love; the women have much in common, and Mary and Elizabeth are reluctant foes, but foes nonetheless, each positioned by birth and fate to destroy all the other holds dear.

Caterina trama alle spalle di Maria per farla cadere, quando il destino la fa alleare alla più acerrima nemica della giovane: Elisabetta.