Wilson was born in Mayfield, Kentucky. In 1916 he began attending Kentucky State College, moving in 1919 to study at the Chicago Art Institute. In 1928 he moved to Harlem, New York, where he joined the Harlem Artists Guild and worked at a brokerage house. From 1941 to 1944 he worked in an aircraft engine factory. He was also commissioned to create triptychs for US Army and Navy chaplains. In 1944 he was awarded a Guggenheim Fellowship and subsequently travelled through the southern United States. In 1952 he travelled to Haiti, an experience that resulted in numerous paintings.
Although Wilson had several exhibitions and won several prizes for his paintings he never became wealthy. He died on either January 1 or 2, 1977, and was buried in a pauper's grave. The exact date of his death and site of his grave are unknown.
Ellis Wilson's painting "Funeral Procession" was featured in the American television NBC sitcom The Cosby Show, in Season 2, "The Auction". In this episode, Clair Huxtable, played by Phylicia Rashad, bids on the painting by her great-uncle (Ellis Wilson) and she wins the auction. The painting then remains in the Huxtable living-room throughout the series.