Russell was born in 1905 in Sandhurst in Berkshire, where his father was an instructor at the Royal Military Academy. Russell became a fan of science fiction, and in 1934 while living near Liverpool he saw a letter in Amazing Stories written by Leslie J. Johnson, another reader from the same area. Russell met up with Johnson, who encouraged him to embark on a writing career. Together, the two men wrote the novella "Seeker of Tomorrow" which was published in Astounding in July 1937. Both Russell and Johnson became members of the British Interplanetary Society.

Russell's first novel was Sinister Barrier, published in the first issue of Astounding's short-lived sister magazine Unknown (March 1939). This is an explicitly Fortean tale based (as Russell explains in the novel's foreword) on Charles Fort's famous speculation "I think we're property". An often-repeated legend has it that Campbell, on receiving the manuscript for Sinister Barrier, created Unknown primarily as a vehicle for the short novel. There is no real evidence for this, in spite of a statement to that effect in the first volume of Isaac Asimov's autobiography, In Memory Yet Green.

His second novel, Dreadful Sanctuary (serialized in Astounding during 1948) is an early example of conspiracy fiction, in which a paranoid delusion of global proportions is perpetuated by a small but powerful secret society.

After serving with the Royal Air Force during World War II and working briefly as an engineer, Russell took up writing full-time in the late 1940s. He became an active member of British science fiction fandom and the British representative of the Fortean Society. He won the first Hugo Award for Best Short Story in 1955 for his humorous short story "Allamagoosa".

Russell was awarded a posthumous Prometheus Hall of Fame award in 1985 for his novel The Great Explosion, and in 2000 he was inducted into the Science Fiction and Fantasy Hall of Fame.

Into Your Tent, a thorough and detailed biography of Russell by John L. Ingham, was published in 2009 by Plantech (UK).

Russell's full-length fiction includes the following:

• Sinister Barrier (1939)
• Dreadful Sanctuary (1948)
• Sentinels from Space (1953), based on the earlier magazine story The Star Watchers (1951)
• Allamagoosa (1955), short story, won The Hugo Award for Best Short Story
• Three to Conquer (1956), based on the earlier magazine serial Call Him Dead (1955)
• Men, Martians and Machines (1955), containing four related novellas
• Wasp (1958)
• Next of Kin (1959), published earlier as The Space Willies (1958)
• The Great Explosion (1962)
• With A Strange Device (1964), also published as The Mindwarpers.

Russell also wrote a large number of shorter works, many of which have been reprinted in collections such as Deep Space (1954), Six Worlds Yonder (1958), Far Stars (1961), Dark Tides (1962) and Somewhere a Voice (1965). His non-fiction includes a compendium of Forteana entitled Great World Mysteries (1957) as well as The Rabble Rousers (1963), a sardonic look at human folly including the Dreyfus affair and the Florida land boom.

Two omnibus collections of Russell's science fiction are available from NESFA Press: Major Ingredients (2000), containing 30 of his short stories, and Entities (2001) containing five novels.

The 1995 novel Design for Great-Day, published as by Alan Dean Foster and Eric Frank Russell, is an expansion by Foster of a 1953 short story of the same name by Russell.

Russell had an easy-going, colloquial writing style that was influenced in part by American "hard-boiled" detective fiction of the kind popularized by Black Mask magazine. Although British, Russell wrote predominantly for an American audience, and was often assumed to be American by readers.

Much of Russell's science fiction is based on what might be described as "Fortean" themes, with Sinister Barrier and Dreadful Sanctuary being the most notable examples. Another common theme is that of the single resourceful human pitted against a ponderous alien bureaucracy -- this is the basis for the novels Wasp and Next of Kin, as well as several shorter works.

Russell is sometimes categorized as a humorous writer, and Brian Aldiss describes him as John W. Campbell's "licensed jester". However, Russell's humour generally has a satirical edge, often aimed at authority and bureaucracy in its various forms. On other occasions, for example in the short stories "Somewhere a Voice" and "The Army Comes to Venus", his work has a deeper and more serious tone, in which the spiritual aspects of humanity's endeavours and aspirations shine through.

Russell's short story "Jay Score" (1941) is unusual amongst the pulp fiction of its time in presenting a black character, the ship's doctor, without any racial stereotyping. Indeed, this story and its sequels (collected in Men, Martians and Machines) may be considered an early example of the science fiction sub-genre in which a spaceship is crewed by a multi-ethnic, mixed human/non-human, complement (cf. the much later Star Trek).

Russell also appears to have originated the colloquialism "myob" for "Mind your own business", which appears frequently in the novella "...And Then There Were None" (Astounding, June 1951) and in the novel The Great Explosion based upon it.

Judgment Day by James Cameron variegates and copiously crayons the plot of Russell`s novella Legwork, in which an extra-terrestrial being irritates men by giving itself the exterior of different of his potential victims, but is finally terminated by them after hard detail work.

“When one is fighting a paper-war one uses paper-war tactics that in the long run can be just as lethal as high explosive. And the tactics are not limited in scope by use of one material. The said material is very variable in form. Paper can convey a private warning, a public threat, secret temptation, open defiance; wall-bills, window-stickers, leaflets dropped by the thousands from the roof-tops, cards left on seats or slipped into pockets and purses money.”- Wasp, p. 75 of 1957 paperback edition