According to the artist, his formative education in art was “autodidact”--self-taught. Middleton developed an affinity for sketching in high school. However, from 1947–1948, his interest shifted to painting.

“For Middleton, who used Elmer’s Glue, collage was quintessentially and formatively European, and his own collage paintings are expressions of the internationalist, indeed democratic, imprint he achieved by leaving the United States.” Beginning in 1944, Middleton traveled to back and forth between his loft in Greenwich Village, New York and several countries a member of the Merchant Marines. His place of refuge between voyages was a rented a loft in Greenwich Village, where he encountered luminaries such as, Walter Williams, Herb Gentry, Franz Kline and Robert Motherwell. Middleton was known to frequent a few of local jazz hot spots where some of jazz greats such as Dizzy Gillespie, Charlie Parker, Thelonious Monk, and John Coltrane hung out.

In 1956, Middleton received a scholarship to study in Mexico, for one year of study at the Instituto Allende in San Miguel de Allende. This opportunity was, according to the artist his “first important break.” Middleton moved to Mexico in 1955 after serving in the Merchant Marine. Inspired by the example of Elizabeth Catlett, he studied at the Instituto de Allende in San Miguel de Allende in 1957. He also had his first one man exhibition at Mexico City’s Galeria Excelsior that same year.

The exposure helped Middleton to consolidate a stylistic and technical evolutions in his work. Up to that time, Middleton had painted in oils and his subject matter was largely figurative images. Middleton, however, began working with collage--repurposed discarded advertisements for bullfights. There were also other noticeable shifts in the artist’s stylistic tendencies. Middle embraced social realism and expressionism. He also adopted a more extemporaneous approach—juxtaposing bold strokes of color, contrast, and fragmented paper with organic paint splashes and various typefaces all of which became proprietary to Middleton’s ouevre.

In addition to his travels to Mexico, Middleton visited several other countries, including Spain, Sweeden, and Denmark. He left the United States permanently in 1959, settling in the Schagen (Netherlands), a place he called home for over forty-years. Middleton’s sojourn there was at critical period in US history during the turbulence of racial unrest of the civil rights era. He found welcome respite at the Royal Academy of Art in Hertogenbosch, where he taught and exhibited regularly across Scandinavia during in the 1960s, 70s, and 80s. In 2003, a retrospective of Middleton’s work was held at the Cobra Museum voor Moderne Kunst.

At the time of his death on July 19, 2015, Middleton’s 1960 collage painting, "Out Chorus," was on view at the Whitney Museum of American Art. The inclusion of his work in this exhibition, underscores its importance “in prevailing canonical artistic traditions of twentieth-century European modernism, particularly the innovation and creative experimentation inherent to collage.”