Jan D'Esopo was born in New York City and the family later moved to Hartford, Connecticut. In 1943, at the age of nine, Jan won various awards in painting at an exhibition held at the Wadsworth Atheneum. Her art career had been launched. D'Esopo spent some summer vacations in Puerto Rico, where her uncle used to work for Puerto Rican governor Luis Muñoz Marín. In 1956, she enrolled and attended Bennington College in Vermont. She graduated with majors in painting and sculpture. She also studied at the Yale School of Fine Arts.
In 1961, D'Esopo and her husband purchased an eighteenth century Spanish colonial house located on Norzagaray Street in Old San Juan. The couple restored the house, which is now known as "The Gallery Inn", and converted it into a gallery, studio, and home. In the gallery, D'Esopo exhibits her works of art and sculptures. D'Esopo developed her own unique style of watercolor painting and in 1985 her paintings were exhibited, with that of other artists from around the world, at the Bronx Museum of the Arts. Her bronze monuments are exhibited in front of the Capitol Building of Puerto Rico and other public and private buildings.