Henry was born in the Royal Château de Saint-Germain-en-Laye, near Paris, the son of Francis I and Claude de France (daughter of Louis XII of France and Anne, Duchess of Brittany). With his brother, he spent three years in Spain as a hostage to Charles V, Holy Roman Emperor, as surety for his father, who had been captured at the Battle of Pavia. Henry married Catherine de' Medici (13 April 1519 – 5 January 1589) on 28 October 1533, when both were fourteen years old.

The following year he became involved with the thirty-five-year-old widow Diane de Poitiers. They had always been very close: she had publicly embraced him on the day he set off to Spain; and during a jousting tournament he had insisted that his lance carry her ribbon instead of his wife's. Diane became Henry's most trusted confidante and for the next twenty-five years wielded considerable influence behind the scenes, even signing royal documents. Extremely confident, mature and intelligent, she left Catherine powerless to intervene. She did, however, insist that Henry sleep with his wife in order to produce heirs to the throne.

When his elder brother Francis died in 1536 after a game of tennis, Henry became heir to the throne; he succeeded his father on his 28th birthday, 31 March, 1547 and was crowned King of France on 25 July 1547 at Reims.