Serle was born to English parents in Elsternwick, Victoria and for many years worked in a life assurance office before in November 1910 becoming chief clerk and accountant at the University of Melbourne. He married artist Dora Beatrice Hake on 29 March 1910. They were to have three children. One son, Alan Geoffrey Serle, was selected as 1947 Victorian Rhodes scholar.
Serle ran a second-hand bookshop during the depression; was guide-lecturer at the National Gallery of Victoria; curator of the Art Museum of the Gallery; and member of the council of the Victorian Artists Society. He was also president of the Australian Literature Society.
Serle's publications included an edition, with notes, of A Song to David and Other Poems by the 18th-century English poet, Christopher Smart; A Bibliography of Australasian Poetry and Verse: Australia and New Zealand; An Australasian Anthology (with 'Furnley Maurice' and R. H. Croll); A selection of Poems by Furnley Maurice; Dictionary of Australian Biography; and A Primer of Collecting.
The Dictionary took more than twenty years to complete and contains more than one thousand biographies of prominent Australians or persons closely connected with Australia. Serle comments in the Preface that "I have endeavoured to make the book worthy of its subject. It would have been better could I have spent another five years on it, but at seventy-five years of age one realizes there is a time to make an end." He was awarded the Australian Literature Society Gold Medal for 1949 for this work.
Serle died in Hawthorn, Victoria, aged 80 on 16 December 1951.