- Claire Foy as Princess Elizabeth and later Queen Elizabeth II.
- Matt Smith as Prince Philip, Duke of Edinburgh, Elizabeth's husband
- Vanessa Kirby as Princess Margaret, Elizabeth's younger sister.
- Eileen Atkins as Queen Mary, Elizabeth's grandmother (season 1)
- Jeremy Northam as Anthony Eden, Churchill's Foreign Secretary, who succeeds him as Prime Minister
- Victoria Hamilton as Queen Elizabeth, George VI's wife and Elizabeth's mother, known as Queen Elizabeth The Queen Mother during her daughter's reign
- Ben Miles as Group Captain Peter Townsend, George VI's equerry, who hopes to marry Princess Margaret
- Greg Wise as Louis Mountbatten, 1st Earl Mountbatten of Burma, Philip's ambitious uncle and great-grandson of Queen Victoria
- Jared Harris as King George VI, Elizabeth's father, known to his family as Bertie
- John Lithgow as Winston Churchill, the Queen's first Prime Minister
- Alex Jennings as the Duke of Windsor, formerly King Edward VIII, who abdicated in favour of his younger brother Bertie to marry Wallis Simpson; known to his family as David
- Lia Williams as the Duchess of Windsor, Edward's American wife
- Anton Lesser as Harold Macmillan, who follows Anthony Eden as Prime Minister (season 2)
- Matthew Goode as Antony Armstrong-Jones, known as Tony, a society photographer who marries Princess Margaret (season 2)
The below actors are credited in the opening titles of single episodes in which they play a significant role.