Mose began painting in the late 1960's after an accident left him crippled and unable to work. Encouraged by his former boss, he began to paint, mostly pictures of flowers, of which he is so fond (Mose is an avid gardener). In the 1970's, Mose would set his paintings out in his front yard to dry, and he began to sell them to passers by. In 1981 he had a one-man show at the Montgomery Museum of Fine Arts, and the next year he was brought to national attention through the Corcoran Gallery of Art's exhibit of "Black Folk Art In America, 1930-1980" in Washington D.C.

Mose Tolliver's pictures of birds and flowers, as well as portrait's and "nasty" paintings, girls on big phallic tricycles, have made him one the most collected and well known of the contemporary folk artists. His work is in museums, galleries, and collections across the United States, and he is included in nearly every book written about the genre.