After serving as a young AIF soldier in the first world war, Johnson returned to Australia and worked at Dymocks Booksellers in Sydney, initially as a junior shop assistant. He had "an unerring instinct for first editions, with an expert knowledge of values" (Smith's Weekly, 30 October 1937). As early as 1922, he was writing on literature in the Sydney Morning Herald (28 January 1922).

Well-connected with a group of emerging artistic and literary giants, he published the anthology Poetry in Australia (1923) and co-founded the journal Vision with Jack Lindsay and Kenneth Slessor in 1923. While the journal lasted only four issues, it was influential.

Around 1930, Johnson returned to publishing, initially under his own name as Frank C. Johnson, before establishing Macquarie Head Press in 1932 and ultimately reverting to Frank C Johnson around 1937. It was a diverse program of publishing, including humour, plays, novels, poetry, art and children's books. Most significantly, he published Slessor's innovative Darlinghurst Nights (1933), which focused on urban life at a time Australian literature was obsessed with rural themes, and Five Bells (1939), dedicated to the memory of cartoonist Joe Lynch.

Alongside its book publishing, Macquarie Head published the magazine The Australian Outline: Books, Authors, Music, Art, Stories & the Theatre (1933-1934). Johnson followed up with a more successful magazine Tempo: The Australian Musical News-Magazine (1937-1956), continued in Tempo and Television (1957-1960). He was also associated with Nicholson's The Music-Maker (1947-1972).

Between 1938 and 1943, Johnson regularly provided illustrations for fiction and occasionally covers for The World's News.

In July 1940, after the Australian government imposed war-time import restrictions, Johnson created a line of Australian-produced comics, drawing on his connections to established newspaper artists such as Unk White and Emile Mercier. Most of the early comics were written by Alfred Charles Headley.

Due to newsprint restrictions, his comics were one-shot titles, beginning with Amazing, released July 1941, followed weekly releases of ever changing titles. While technically one-shots, they operated as four on-going series, with the stories in Amazing continued a month later in Thrilling, then Victory and Hot Shot; and the same with Star, Marvel and Magic. When creativity for new titles ran out, old titles were reused by adding "new"—New Crash, New Magic etc.

In late 1941, Johnson introduced the Magpie Series of reprinted Australian writing, with the first three books composed of stereotypical outback yarns by John Crothers. It ran until 1949, with a second series beginning soon after and running until the mid 1950s. While the earlier Macquarie Head brand had reflected the well-know Shakespeare Head publisher, the Magpie series mimicked the design of Penguin books.

The monthly magazine, Famous Detective Stories (1946-1954), was one of Johnson's most successful ventures, providing true Australian crime and detective short fiction. A 'new series' of seven Famous Detective Stories was part of the Magpie Books (second series) around 1955.

Johnson also did the short run western series, Sure Fire Westerns (1947-1950), and sporting-themed series Kings of the Turf (1947-1950) and Sporting Novels (1950).

A final magazine publishing ventures was Teenage (~1959), which attempted to capture the youth culture market with pin-ups, pictures and stories of music stars.

Johnson's publishing work was largely a one-man company, based on his interests and connections. It did not survive his death and all publishing ceased in 1960.