Along with his brother Reb Spikes, John ran a traveling show band in early 1900s. At one point, Jelly Roll Morton was a member of the band. In around 1915, the Spikes were performing in San Francisco under the name The Original So-Different Orchestra, with Reb Spikes billed as the "World's Greatest Saxophonist".
Around 1919, they then settled in Los Angeles, where they started a music store, a nightclub, an agency and a publishing house.
They were the first to record an all-black jazz band in 1922. In 1927, they shot a short sound film that predated The Jazz Singer, the first full-length sound film. Their most enduring musical collaborations were writing the lyrics to Morton's Wolverine Blues and their own composition, Someday Sweetheart, which has become a jazz standard.