Between the sixth and third century BC was erected an imposing city walls (the so-called “megalithic walls”), which are visible today in some parts of Altamura. From the following century, the city experienced a substantial decline, and it was only in the Middle Ages that Altamura regained some importance, thanks to Emperor Frederick II of Swabia (1194-1250), who re-made the city, repopulating and calling it "Altamura" for the presence of high megalithic walls.

Many residents of the surrounding areas arrived in the new city , as also Greeks and Jews, the last of which still occupied a district called "Giudecca" , where they built a synagogue. Frederick II ordered the construction of the Cathedral (1232), destined to become one of the most revered shrines of Puglia.

The territory of Altamura was the domain of various noble families, in particular of the Orsini del Balzo and  Farnese (1538-1734), who built numerous palaces and churches. In 1734, after the marriage of Philip V (1683-1746) of Spain and Elisabetta Farnese (1692-1766), the city passed under the Bourbon; in the Napoleonic time it became a Republic, but the intervention of the Papal troops commanded by Cardinal Fabrizio Ruffo (1744-1827) brought the city under the Dominion of the Papal States.

Altamura remained to the Bourbon until unification to the Kingdom of Italy (1861).

Etymology

It is said that Altamura, in ancient times, was known as "Altilia", a name that, according to some scholars of the nineteenth century, derives from "Altea", Queen of the Myrmidons, who, arrived here after the death of her son Meleager, would founded the city, which  derived its name by her. This hypothesis seemed strengthened by Latin verses engraved on a plaque on the door of the San Lorenzo Church 'extra moenia' ('outside the walls'), which say: “Mirmidonum genti sit laus et coelica vita” [“Both praise and Divine life to the noble lineage of Myrmidons”]. Apart of the fabulous story,  there is the fundamental fact that the name "Altilia", "[...] is not attested by the ancient authors and Chiovilli conjectures that it derives from the Germanic 'al-teil' ('the ancient part'), a name imposed by Alzeco (7th century AD), the Duke of the Bulgarians, who, according to Paul the Deacon (720-700), would have had in granting those  spacious and deserts places in 663 AD [...] "(See" Cultura e Scuola", 1993, p. 225).

The name results from “altu” ("high"), (like other names derived from adjectives): “Atamura is so called for its 'cyclopean' walls” (See G.B. Pellegrini, “Toponomastica Italiana” ["Italian toponymy"], Hoepli 1990: 236). It is said that the Emperor even named it  "Alta Augusta,"