Ortonovo's history is strictly linked to the one of the Roman town Luni, which also gives the name to the whole region Lunigiana. The name Luni in turns comes from Luna ("Moon"), a Roman goddess much venerated in the area. In the post-Roman period Ortonovo went through different masters: the Byzantine, the Longobard, the Norman and even the Saracen domination.

Around year 1000 Ortonovo territory was annexed to the town of Sarzana; at the same time, Ortonovo was under the influence of the bishop of Luni, although it enjoyed the status of "comune libero" ("free city"). In the XIII century Enrico da Fucecchio promoted the reinforcement of the castle and the construction of stronger walls; in addiction, he regulated cattle-breeding and agriculture, enlarged the boundaries of the town's possessions and, in 1285, obtained for Ortonovo the right to mint coins.

After the death of Enrico da Fucecchio, Ortonovo fell under the rule of Pisa; later, following the territorial division wanted by Castruccio Castracani, the town of Lucca became Ortonovo's new master. At the end of the XIV century Ortonovo became part of the Visconti possessions, to later join the Repubblica Fiorentina and remain part of it throughout the XV century. After Charles VIII took Florence, Ortonovo was sold for a large amount of money to the Banco di S. Antonio. In 1562 Ortonovo fell under the rule of the Repubblica Genovese and clashed against Sarzana about rights over the Luni region and over the coast nearby. A law edited in 1683 sanctioned the victory of Sarzana, which obtained the right to cultivate and build on the land contended for; this right was maintained by Sarzana until the Unità d'Italia (Italian Reunification, second half of XIX century).