John Morse showed an early interest in art and at age 11 was invited to join twice-weekly evening oil painting classes for adults in the small Southern town of his childhood, Lake City, Florida. He attended for four years and soon earned commissions painting portraits, landscapes and murals. From the age of 15 he worked as a sign painter, including interstate billboards. At 16, he left home and moved to the Oregon coast where he worked on poster arts and super-graphic murals. With the exception of high school art classes, he received no further formal art training.

In 1981, he moved to Barcelona where he painted and sold watercolors of street scenes. When funds for materials ran low, he often created collage landscapes and portraits from found papers, usually litter. Soon, he was hired as art director at Diagonal, a leading art and culture magazine of Spain. While in Barcelona, he and fellow expatriate Brice Hammack formed Chi-Perro Studios, creating art from disposable plastic, including trash bags, grocery sacks and plastic wrap.

In 1982, Morse returned to America, arriving for the first time in New York City, his new home. From 1984 to 1988, he produced "A-R-T," a silent, 30-minute program on Manhattan Cable Television that each week presented a single screen image intended to convert the television into a sculptural box (the first episode offered the interior of an oven baking a chicken).

From 1986 to 2000, John Morse served on the founding board of directors of Socrates Sculpture Park while it was transformed from an abandoned landfill into an international sculpture center, dedicated to the exhibition of monumental work. Over the years, he created several works for the park, including opening day installations, flag sculptures and a mural that still stands at the park's eastern edge. Socrates is now part of the New York City Parks Department.

His collages, sculptures, installations, watercolors and drawings have been exhibited at the Kentler International Drawing Space, Brooklyn; Islip Art Museum, Islip, New York; the DUMBO Art Center, Brooklyn; and Match Fine Print, New York City, as well as galleries across the United States. His collage is represented by Maxwell Gallery in Atlanta and Scoop Gallery in Charleston, South Carolina and currently also hangs at Silas Marder Gallery in Bridgehampton, New York.

His work is in the private collections of, among others, sculptor Mark di Suvero; New York Commissioner of Cultural Affairs, Kate Levin; New York Commissioner of Transportation, Janette Sadik-Khan; installation artist and sculptor Eve Sussman; Elizabeth Gilbert, author of Eat, Pray, Love; and Jacques d'Amboise, founder of the National Dance Institute.

Morse is also a prolific writer, having written several non-fiction titles published by Monacelli Press, McGraw-Hill, Henry Holt and Random House. In 2005 he created 39 original collages for Categories: On the Beauty of Physics, published by Vernacular Press and described by Raina A. Lampkins-Fielder of the Whitney Museum of Art as "a creative and liberating journey of the mind." In 2010, ten of his haiku poems were featured on 500 'bandit' signs posted around the streets of Atlanta, a guerilla installation that received extensive press coverage including The New Yorker, The Guardian, NPR and South Africa National Radio.