Domenico "Mimmo" Paladino was born on December 18, 1948, in Paduli, near Benevento, Italy, and grew up in Naples. He developed an early interest in art through the influence of an uncle who was a painter. At the beginning of the 1970s he began to concentrate on drawing, introducing mythological subject matter that would later be of major importance to his work. His work draws on a wide range of archeological, mythological and stylistic sources, including Egyptian, Etruscan, Greco-Roman, early Christian, and Romanesque art, regarding all of them as legitimate sources in a non-hierarchical manner.

In addition to drawing and painting, Paladino has become prolific in a variety of media, including sculpture and various types of incision. Between 1978 and 1980, he created monochrome paintings using primary colors, to which he attached geometric elements and found objects, such as twigs and masks. By 1983 he was attaching sculptural forms—usually in carved wood—to his canvases, lending a fetishistic quality to them. In the early 1980s he began to recreate his archaic personages in bronze using colored patinas, and to carve in wood and stone, creating totemic objects and masks as well as truncated animals and human figures. His work, in its proliferation of techniques and sources, blurs the distinctions between sculpture and painting, creating a dialogue between traditional and minimal modes of representation.

In 1980, art critic Achille Bonito Oliva included Palladino in the Aperto 80 exhibition at the Venice Biennale, thus grouping him with other Italian artists of his generation, such as Sandro Chia, Francesco Clemente, Enzo Cucchi and Nicola De Maria, and naming them the Transavanguardia Italiana. Paladino has exhibited extensively throughout Europe, North and South America, and Asia. Paladino lives and works in Paduli and Milan.