Through his maternal grandfather, he was a descendant of Lucrezia Borgia and Pope Alexander VI.
In 1576 he founded the Catholic League to prevent the heir, King Henry of Navarre, head of the Huguenot movement, from succeeding to the French throne.
A key figure in the French Wars of Religion, he was one of the namesakes of the War of the Three Henrys.
A powerful opponent of the queen mother, Catherine de' Medici, he was assassinated by the bodyguards of her son, King Henry III.