It is an important industrial and artistic center in the floodplain on the left (north) bank of the Esino river, 17 kilometres (11 mi) before its mouth on the Adriatic Sea.

During the fall of the Western Roman Empire, Jesi was ravaged by the troops of Odoacer (476 AD) and again in 493 by the Ostrogoths of Theodoric the Great.

After the Gothic War, Italy became part of the Byzantine Empire, and Jesi became one of the main centers of the new rulers, and a diocese seat.

In December 1194 the future Holy Roman Emperor Frederick II was born here:[3] he later made Jesi a "Royal City".

In the 14th century it was captured by the Papal vicar Filippo Simonetti, then by Galeotto I Malatesta (1347–1351), by Braccio da Montone in 1408, and by Francesco I Sforza, who turned it into his family's main stronghold in the Marche.