Clive James was born and schooled in Sydney. After attending Sydney Technical High School, he completed a Bachelor of Arts at the University of Sydney. Associated with the Sydney Push during his university years, he was literary editor of Honi Soit and an active participant in student life. After graduating in 1961, he worked as an assistant editor at the Sydney Morning Herald.

In 1962, James moved to England. He has remained an expatriate in the years since. After a period in London, he pursued a second degree at Pembroke College (Cambridge University), where he read English literature. Here he edited several magazines and, in 1966, won election to the presidency of Cambridge's illustrious revue company, Footlights.

Following his university education, James worked as a freelance writer and, from 1972 to 1982, was a television critic for the Observer. James began his successful BBC television career in 1983 with The Late Clive James and also appeared in such shows as Clive James on Television and Saturday Night People. Since then, his various television shows have offered viewers performances, travelogues and interviews. Most recently, James has embraced the internet to circulate his interviews and offer advice for Australians travelling in Britain.

Since the early 1970s, James has published poetry, several collections of criticism, travel writing, novels and several volumes of autobiography. In the 1970s, he also collaborated on six album with British singer-songwriter Pete Atkins, which enjoyed a revival in the early 2000s. While he is not often acknowledged for the quality of his exuberant writing, his style and humour, which some regard as quintessentially Australian, ensure that he remains an important member of a small group of high-profile expatriates.

In 2013, Picador published James' translation of Dante's The Divine Comedy. He has since published a number of other works, including the poetry collections Sentenced to Life (2015) and Injury Time (2017) and collections of non-fiction.

James was diagnosed with leukaemia and emphysema in 2010, and died at his home in Cambridge in November 2019.