MacInnes was born in London, the son of singer James Campbell McInnes and novelist Angela Thirkell, who was also related to Rudyard Kipling and Stanley Baldwin. His family moved to Australia in 1920, MacInness returning in 1930. For much of his childhood, he was known as Colin Thirkell, the surname of his mother's second husband; later he used his father's name McInnes, afterwards changing to MacInnes.

He worked in Brussels from 1930 to 1935, then studied painting in London at the London Polytechnic and the School of Drawing and Painting in Euston Road. He served in the British intelligence corps during World War II, and worked in occupied Germany after VE Day. This led to his first novel, To The Victors The Spoils. Following his return to England, he worked for BBC Radio until he could earn a living from his writing.

He was the author of a number of books depicting London youth and black immigrant culture during the 1950s, in particular City of Spades (1957), Absolute Beginners (1959) and Mr. Love and Justice (1960). Many of his books were set in the Notting Hill area of London, then a poor and racially mixed area, home to many new immigrants and which suffered race riots in 1958. Openly bisexual, he wrote on subjects such as urban squalor, racial issues, bisexuality, drugs, anarchy, and "decadence."

Mr. Love and Justice follows two characters, Frank Love and Edward Justice, in late 50s London. Mr. Love is a novice ponce (pimp); Mr. Justice is a cop newly transferred to the plain-clothes division of the Vice Squad. Gradually their lives intermesh. The title of the novel was used for a 2008 album, Mr. Love & Justice, by Billy Bragg. Bragg's previous album England, Half English was also named after a MacInnes book.

Absolute Beginners was filmed in 1986 by director Julien Temple.[1] In 2007 a stage adaptation by Roy Williams was performed at the Lyric Theatre, Hammersmith, London.

MacInnes occurs as a character in Tainted Love, Stewart Home's novel of 1960s and 1970s counterculture.