Francesco Paolo Michetti learned painting's rudiments from a local fresco painter. In 1868 he traveled to Naples, supported by a small grant to study at the academy there. Asserting that his temperament would benefit more from real life situations, he was allowed to return to the Abruzzo region in 1869 and continued to receive his grant.
Michetti exhibited at the Paris Salons of 1872 and 1875, but he also belonged to Scuola di Resina, a group of Neapolitan painters that aimed to bring Italian art into Europe's mainstream. Abruzzo was his emotional and aesthetic inspiration. He captured its people, animals, and local events in emotionally charged paintings with luminous colors and vibrant light. In 1883 Michetti purchased a convent as his home and studio. For the next twenty years, the convent was a meeting place for Abruzzo's artists and exponents of culture, including writer Gabriele D'Annunzio. Michetti's 1895 Daughter of Iorioinspired D'Annunzio's 1904 tragedy, for which Michetti designed the sets and costumes.
From 1872 onward, Michetti also produced small, decorative clay sculptures. After a lukewarm response to his paintings at the 1900 Exposition Universelle in Paris, he abandoned painting, sold his studio, and generally lived as a recluse.