Upfield was born in Gosport, Hampshire, England on 1 September 1890. His father was a draper. In 1910, after doing poorly in examinations towards becoming a real estate agent, Upfield was sent to Australia by his father.

With the outbreak of World War I, he joined the First Australian Imperial Force on 23 August 1914. Upfield sailed from Brisbane on the HMAT Anglo Egyptian on 24 September 1914 to Melbourne. At the time of sailing he had the rank of Driver and was with the 1st Light horse Brigade Train (5 Company ASC [Army Service Corps]). In Melbourne he was at a camp for several weeks before sailing to Egypt. He fought at Gallipoli and in France, and married an Australian nurse, Ann Douglass, in Egypt in 1915. He was discharged in England on 15 October 1919. He worked as a private secretary to an army officer. In 1921 he returned to Australia with his wife and their son.

For most of the next twenty years he travelled throughout the outback working at a number of jobs. He learnt much of Aboriginal culture, later to be used in his books.

Upfield created the character of Detective Inspector Napoleon Bonaparte, based on a man known as 'Tracker Leon' whom he had met in his travels. Leon Wood was a "half-caste" (in the language of the day) Aboriginal man who was employed as a tracker by the Queensland Police. The novels featuring 'Bony', as the character was also known, were far more successful than other Upfield writings.

Late in life Upfield became a prominent member of the Australian Geological Society, involved in scientific expeditions. In particular he led a major expedition in 1948 to northern and western parts of Australia, including the Wolfe Creek crater. The Wolfe Creek crater was a setting for his novel The Will of the Tribe published in 1962.

After living at Bermagui, New South Wales, Upfield moved to Jasmine Street, Bowral, New South Wales. Upfield died at Bowral on 13 February 1964. His last work, The Lake Frome Monster, published in 1966, was completed by J.L. Price and Dorothy Stange.

In 1957, his defacto Jessica Hawke, published a biography of the author entitled Follow My Dust!. It is generally held however, that this was written by Upfield himself.

Upfield's novels were held in high regard by some fellow writers. In 1987, H.R.F. Keating included The Sands of Windee (1931) in his list of the 100 best crime and mystery books ever published. J.B. Priestley wrote of Upfield: "If you like detective stories that are something more than puzzles, that have solid characters and backgrounds, that avoid familiar patterns of crime and detection, then Mr Upfield is your man." Others have found Upfield's prose stilted. Much of the appeal of Arthur Upfield's stories lies in the depiction of outback Australian life in the 1930s through into the 1950s.

In The Sands of Windee, a story about a "perfect murder", Upfield invented a method to destroy carefully all evidence of the crime. Upfield's "Windee method" was used in the Murchison Murders, and Upfield was called to give evidence in court.

Upfield's novels were very popular in America (originally because so many American servicemen stationed in Australia during WWII read them and brought copies back), in England and were also translated into German.

The late US mystery novelist Tony Hillerman was generous in his praise for Upfield's works. In his introduction to the posthumous 1984 reprint of Upfield's A Royal Abduction he described the seduction in his youth of Upfield's crime novels' descriptions of both the harsh outback areas, and "the people who somehow survived upon them ... . When my own Jim Chee of the Navaho Tribal Police unravels a mystery because he understands the ways of his people, when he reads the signs in the sandy bottom of a reservation arroyo, he is walking in the tracks Bony made 50 years ago."

Television series

From 1972 - 1973 a 26-episode television series was produced by Fauna Productions (also responsible for Skippy the Bush Kangaroo). After a long search for a half-white, half-Aborigine actor, the producers chose English actor Jon Finch for the role of Detective Inspector Napoleon Bonaparte. When he suddenly became unavailable, Fauna's John McCallum flew to London in panic, and was lucky enough to audition New Zealand actor James Laurenson on his last day there. Offered the lead role, Laurenson hurriedly flew to Australia, reading "Bony" books all the way over.

The series was called Boney, partly to make the pronunciation of the name more obvious, and partly because that had been Upfield's original intention - a publisher's misprint on the first novel had renamed the character. Most of the episodes were based directly on one of the novels, but there were some adaptations. Two original scripts were not directly based on any novel; five novels were not adapted for television, effectively ‘reserving’ them in case a third series eventuated. At the time, many of the books were reprinted with the spelling altered to ‘Boney’ on the covers (although retaining the original in the text), and featuring a photo from the relevant episode.

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