 Various artifacts and remains dating back to the first half of the second millennium B. C. E. have been found in the northern parts of the Meadow of Medula and the lowlands of Jabalon.Additional archaeological evidence from the "Cerro de las Cabezas" dig further suggests that the region was an important settlement of the Iberian "Oretan" tribe between the 7th and 2nd centuries B. C. E.

In the following centuries, the region came to lie under the sphere of influence of a Roman, and later Visigothic, town near present-day Valdepeñas.The Roman legacy and influence in Santa Cruz are most evident in the region's wine culture and many vineyards.