Lowitja O'Donoghue was born at Granite Downs, a cattle station located on the Stuart Highway in northwest South Australia. Her father, Tom O'Donoghue, was a stockman of Irish descent. Her mother, Lily, was one of the native Yankunytjatjara people. Tom and Lily met while Tom was working at Everard Park, another cattle station on the traditional country of the Yankunytjatjara. The couple moved to Granite Downs, known as Indulkana to the Yankunytjatjara, in 1925. Lowitja was born here around 1 August 1932. She was the fifth of six children.