Lelio Orsi studied with his painter father, but very early on he incorporated into his polished, illusionistic style the two influences that remained primary throughout his life: Giulio Romano's exaggerated movement and excitability and Correggio's poignant passion and vibrant way of seeing. By 1538 Orsi had moved to a larger nearby town, Reggio Emilia, where he painted many architectural facades with illusionistic designs. Accused of involvement in a murder, he returned to his native Novellara in 1546, where he continued to create distinguished decorative works, especially as a painter of facades for the local nobility. Though he also completed a large project for the count of Novellara, providing everything from architectural drawings to decorative partitions for a villa, only fragments of any of these works survive.
The year 1554, spent in Rome, was decisive: there he absorbed Michelangelo's Mannerism, which stayed with him for life. He began to concentrate on making easel paintings of mostly mythological and religious subjects; they indicated the energy and expressiveness of his monumental works, and their jeweled technique made them beautiful in themselves. By 1576 Orsi was probably back in Reggio Emilia.