Gruffudd's parents, Peter and Gillian Griffiths, were teachers. His father was headmaster at two Welsh comprehensive schools in South Wales, first at Ysgol Gyfun Llanhari then later at Ysgol Gyfun Rhydfelen. He has two siblings; a brother, Alun, who is two years younger, and a sister, Siwan, who is seven years younger than he is.
After playing Oscar Wilde's lover John Gray in 1997's Wilde he took his first international role as Fifth Officer Harold Lowe in the blockbuster film Titanic. He later landed his best-known role as Horatio Hornblower in Hornblower.
- Hornblower: The Even Chance (1998)
- Hornblower: The Examination for Lieutenant (1998)
- Hornblower: The Duchess and the Devil (1999)
- Hornblower: The Frogs and the Lobsters (1999)
- Hornblower: Mutiny (2001)
- Hornblower: Retribution (2001)
- Hornblower: Loyalty (2003)
- Hornblower: Duty (2003)