Manuello Paganelli grew up in several exotic places such as Santo Domingo, Italy, and Puerto Rico. He went to school in Tennessee and planned to become a medical missionary doctor then shortly after purchasing a camera for the very first time, his life totally changed when he read a magazine article about a great photographer. He was so astonished by this man's life and art that as soon as he finished reading the article he decided to call him.

Manuello dialed information for Carmel by the Sea, California, and that is how his friendship and mentoring with Ansel Adams began. His first photo break came soon after when he landed a job at the Chattanooga Times, and after a couple of years, he went to work in the Washington, DC area.

In 1989 he began to explore Cuba, its land, its people, and its complex relationship with the USA. IN 1995 he had his first solo photo show of his work on Cuba, and that same year earned him a fellowship grant. On reviewing his exhibit the Washington Post wrote "Manuello Paganelli's Cuban photographs are a brilliant window on a land and people too long hidden from North American eyes, Working in the tradition of Cartier-Bresson and Robert Frank, Paganelli brings an artist's eyes and a native son's sensibility to his superb photographs."

In the early 1990s, he started work on his Black Cowboys series, and in March 2009, part of his documentary was featured at the Annenberg Space for Photography. In the summer of 2012, Paganelli was invited for a photo show in St Petersburg, Russia, of his Black Cowboys documentary at the prestigious Manege Museum during the Photo Vernissage 2012.