In 1912, Herbert's family moved from Geraldton to Fremantle and Xavier Herbert began working in a chemist shop while continuing his schooling. Following World War I, and after qualifying as a pharmacist, Herbert moved to Melbourne to study medicine. He studied medicine for one year and worked as a dispenser in a hospital. In 1926 he moved to Sydney before travelling further north, giving up his pharmaceutical and medical careers. In 1927 he was in Darwin, working as a railway fetter. When Herbert left for England in 1930, he had already published a number of short stories, indicating the direction his life was to take.
Herbert wrote a novel, Black Velvet, on the journey to England, but it was considered too coarse by English publishers. In 1931 he met Sadie Norden who encouraged him to pursue his writing and became his wife two years later. In 1932 Herbert completed the novel, Capricornia, but it was rejected by English publishers as too long. Herbert returned to Australia that year, bringing the manuscript with him. After some shortening and revision it was eventually published in 1938. Capricornia received a number of awards and remains Herbert's most admired work. It was first received primarily as a social protest against the treatment of Aboriginal Australians by European Australians, but later critics revealed the technical brilliance of the narrative. Herbert spent the next fifty years trying to write another comparable novel. After a number of failures, he published Poor Fellow My Country to great acclaim in 1978.
Herbert became a vocal supporter of the Land Rights Movement in the 1970s, reflecting the affection for and understanding of Aboriginal Australians that he had developed in his youth and travels. In the early 1980s after rejecting the award of AO because of his republican leanings, he began work on another novel that was meant to continue the criticism of Australian society that his two famous novels had begun. On a writing trip to Alice Springs the ageing and frail Herbert became ill. He died there in November 1984.