Henry Ian Cusick Chávez was born in Trujillo, Peru to a Peruvian mother and a Scottish-Irish father. Living in Trujillo for two years, his family moved to Spain, then Scotland and lived in Trinidad and Tobago for ten years.

There he attended Presentation College. He moved back to Scotland at the age of fifteen. Cusick spent six months at the Royal Scottish Academy of Music and Drama in Glasgow and then joined the Citizens' Theatre. He is fluent in both English and Spanish, and was raised Roman Catholic.

Cusick began his career as a classical theatre actor. His first leading roles on stage included: Dorian Gray in The Picture of Dorian Gray with Rupert Everett, Hamlet in The Marovitz Hamlet with Helen Baxendale, and Horner in The Country Wife.

His performances as Torquato Tasso in the Edinburgh International Festival production of Torquato Tasso, and Creon in the Citizens' Theatre production of Oedipus earned him a special commendation for the Ian Charleson Award 1995 for outstanding performance by a young actor in a classical theatre role.

Cusick then began taking television and film roles. After appearing in recurring roles in shows such as Casualty and The Book Group, he starred as Jesus Christ in the 2003 film The Visual Bible: The Gospel of John, a word-word re-telling of Saint John's Gospel.

His largest role to date came in 2005 when he was cast as Desmond Hume in the ABC series Lost. Originally a recurring guest star in the second season (for which he received an Emmy nomination), Cusick became a member of the main cast from season three onwards.

Cusick won the role when, while staying at the home of his friend Brian Cox, he met Cox's next-door neighbor Carlton Cuse, the executive producer of Lost. Cusick believes: "a seed (was) planted, because they had been looking for either a Scottish or Irish character.