The song was originally to be called "Cameo Chameleon". The band were recorded in interviews in late 1983 stating this was to be the title of their next single.[citation needed] The B-side of Karma Chameleon is "That's the Way (I'm Only Trying to Help You)" (in an alternate and shorter version). In an interview Boy George explained "The song is about the terrible fear of alienation that people have, the fear of standing up for one thing. It's about trying to suck up to everybody. Basically, if you aren't true, if you don't act like you feel, then you get Karma-justice, that's nature's way of paying you back."
The prominent harmonica part was played by Judd Lander, who had been a member of Merseybeat group The Hideaways in the 1960s. He had also played the harmonica part on Church of the Poison Mind.[2]