Francis Webb was born in Adelaide, but after the death of his mother in 1927, he was raised by his paternal grandparents in Sydney. He attended Catholic schools, completing his high school education with the Christian Brothers in 1942. In 1943 he joined the RAAF and trained as a wireless operator in Canada, but he returned to Australia without seeing any action. After the war, he enrolled in Arts at the University of Sydney. His decision to discontinue his studies after one year and concentrate on his writing proved successful when his first book, A Drum for Ben Boyd (1948), attracted high praise from Douglas Stewart and won the Grace Leven Prize.
Soon after this success, Webb lived in England for a time, and after returning to Australia, held a variety of jobs and published two more books of poetry before 1953. Webb went back to England that year and was hospitalised for varying periods, suffering the effects of mental illness. During this time, Webb produced what many critics regard as his finest poetry. Webb was devoted to the Catholic faith and his search for meaning was conducted with religious fervour. This search often emerged in his work through the motif of exploration. The most striking example is the sequence 'Eyre All Alone' (1961) which reflects Webb's significant interpretations of major characters and events in Australia's history.
Webb returned to Australia in 1960 and continued to suffer the effects of mental illness. Nevertheless, he continued to contribute poetry to journals such as Southerly and Meanjin and he published two more volumes in the 1960s. The Ghost of the Cock (1964) contains the sequence "Ward Two" which powerfully recounts Webb's time in a Parramatta psychiatric centre. In the last years of his life he corresponded regularly with Nan McDonald, Rosemary Dobson and Gwen Harwood.