A diagnosed chronic schizophrenic, Willis gained an enormous cult following in the 1990s. In addition to his large body of solo musical work, Willis fronted the punk rock band the Wesley Willis Fiasco. He was also a visual artist long before his forays into music, and produced hundreds of intricate, unusual, colored ink-pen drawings, most of them of Chicago streetscapes and CTA buses.
On August 21, 2003, at the age of forty, Willis died due to complications from chronic myelogenous leukemia. At the time of his death, he had recorded over 1,000 songs.