Zeta-Jones established herself in Hollywood with roles that highlighted her sex appeal, such as in the action film The Mask of Zorro (1998) and the heist film Entrapment (1999). She received acclaim for her performances as a vengeful pregnant woman in Traffic (2000) and a murderous singer in the musical Chicago (2002); for the latter she won Academy and BAFTA Awards for Best Supporting Actress. She starred in high-profile films for much of the decade, including the black comedy Intolerable Cruelty (2003), the heist film Ocean's Twelve (2004), the comedy The Terminal (2004), and the romantic comedy No Reservations (2007). Parts in smaller-scale features were followed by a decrease in workload, during which she returned to stage and played an ageing actress in A Little Night Music (2009), winning a Tony Award. Zeta-Jones continued to work intermittently in the 2010s, starring in the psychological thriller Side Effects (2013) and the action film Red 2 (2013), and portrayed actress Olivia de Havilland in the FX television series Feud (2017).

Zeta-Jones is the recipient of several accolades, including an Academy Award, a British Academy Film Award and a Tony Award, and in 2010, she was appointed Commander of the Order of the British Empire (CBE) for her film and humanitarian endeavours. She supports various charities and causes, and is a prominent celebrity endorser of brands. Her struggle with depression and bipolar II disorder has been well documented by the media. She is married to American actor Michael Douglas, with whom she has two children.