He is best known for his roles in the films Velvet Goldmine, Bend It Like Beckham, Woody Allen's Match Point and his television roles as Elvis Presley in the biographical miniseries Elvis, which earned him a Golden Globe for Best Actor, and as King Henry VIII in the historical drama The Tudors.

In two of his films, Velvet Goldmine and August Rush, he also took over singing parts.

He has been the face of several advertising campaigns for Hugo Boss fragrances.

Rhys Meyers was born Jonathan Michael Francis O'Keefe in Dublin, Ireland, the son of Geraldine Meyers and musician John O'Keefe. His stage name is derived from his mother's maiden name, Meyers.

Rhys Meyers was born with a serious heart problem and was baptised shortly after his birth, as it was feared he would not survive long enough for a traditional baptism ceremony. He spent the first few months of his life in hospital. Born in Dublin, he moved to Cork City at one year old and was raised there. He has three younger brothers named Jamie, Alan and Paul, who are all professional musicians.

When Rhys Meyers was three years old, his parents separated. His mother raised Rhys Meyers and his brother Alan, while his other two brothers went to live at their grandmother's house with their father.

Rhys Meyers was expelled from the North Monastery Secondary School at age 16 for truancy and spent much of his time hanging out in pool halls. Casting agents looking for Irish boys to appear in War of the Buttons spotted Rhys Meyers at a Cork pool hall, the Victoria Sporting Club, and invited him to audition. Although he was passed over for War of the Buttons, the casting agents encouraged him to pursue a career in acting. His first film role came soon afterwards, in A Man of No Importance (1994). In 1996, he appeared in Michael Collins, as the title character's assassin. In 1999, he appeared in Ride with the Devil as psychopathic guerrilla fighter Pitt Mackeson.

Rhys Meyers has starred in television series including Gormenghast (2000) and in the CBS 4-hour mini-series Elvis (2005) as Elvis Presley alongside Randy Quaid as Colonel Tom Parker and Rose McGowan as Ann-Margret. Meyers did not sing for his role in the miniseries. The latter earned him an Emmy nomination and a Golden Globe win. He has starred in the BBC/Showtime co-production The Tudors (2007) as Henry VIII. He was nominated for the Golden Globe for Best Actor in a Television Drama in 2007 for the role.

His film roles range from a David Bowie-inspired glam rock star in Velvet Goldmine (1998) to a dedicated girls' football coach in Bend It Like Beckham (2002). He appeared in Vanity Fair (2004) opposite Reese Witherspoon. He co-starred opposite Colin Farrell in Oliver Stone's epic Alexander (2004). In 2005, Rhys Meyers starred in Woody Allen's film Match Point, for which he received a Chopard Trophy at the Cannes Film Festival. In 2006, he appeared in Mission: Impossible III. Subsequent projects included August Rush (2007) and The Children of Huang Shi (2008), Shelter, co-starring Julianne Moore, and From Paris with Love (film) (2010), co-starring John Travolta.

Rhys Meyers, a self-taught singer and guitarist, has appeared in a number of musical roles. His first such role was that of rock star Brian Slade in Velvet Goldmine; two of the songs he sang ("Baby's On Fire" and "Tumbling Down") are on the film's soundtrack. He sang briefly in the TV miniseries version of The Magnificent Ambersons, performed in studio scenes of the miniseries Elvis and played the flute in Gormenghast. In the 2007 music drama August Rush, Rhys Meyers performed on-screen as singer-songwriter Louis Connelly and is credited for four songs on the soundtrack – "Break", "Moondance", "Something Inside" and "This Time". Of the four, "This Time" and "Break" were considered in the Best Original Song category of the 80th Academy Awards. "This Time" was not released as a single but peaked at #84 of the Canadian Hot 100.