He was born Geswanouth Slahoot on a First Nations reserve in North Vancouver in 1899. His English name was Dan Slaholt. His last name was changed to George when he entered a residential school at the age of 5. He worked at a number of different jobs including longshoreman, construction worker and school bus driver. He was chief of the Tsleilwaututh (Burrard) Band from 1951 to 1963.

When he was over 60, he got his first job acting in a CBC television series, Cariboo Country, in 1960. He performed the same role in a Walt Disney Studios movie, Smith!, adapted from an episode in this series. At the age of 71, he won several awards for his role in the film Little Big Man, including a nomination for the Academy Award for Best Supporting Actor. He continued to act in other movies, such as The Outlaw Josey Wales and Harry and Tonto, and on television, including the miniseries Centennial, based on the book by James A. Michener.

He performed the role of Rita Joe's father in George Ryga's stage play, The Ecstasy of Rita Joe, in performances held in Vancouver, the National Arts Centre in Ottawa and Washington.

During his acting career, Chief Dan George also worked to promote better understanding by non-natives of First Nations people. His soliloquy, Lament for Confederation, a riveting indictment of the appropriation of native territory by white colonialism, was performed at the city of Vancouver's celebration of the Canadian centennial in 1967; this speech is credited with escalating native political activism in Canada as well as touching off widespread pro-native sentiment among non-natives. In 1971, he was made an Officer of the Order of Canada.