During the Upper Palaeolithic period, the Barbadun basin was home to a group of hunters and gatherers. They had their base camp in the Arenaza cave. The oldest remains found in Muskiz date from a much later period, known as the Aeneolithic-Bronze Age (4th to 3rd millennium BC). By this point, although they continued to practise hunting and gathering, humans were also capable of producing their own food by cultivating crops and keeping farm animals. The groups lived in the open air, in settlements such as the one found at Ilso Betaio (Sopuerta-Arcentales). They worshipped their dead and left behind great open-air funerary constructions (dolmens and tumuli, especially in mountain areas) and burial sites in caves. To date, no evidence has been found in Muskiz of this duality of funerary rites (cave burials are found in the mouth of the Barbadún river, but the nearest dolmens are some 8 kilometres away at Alen-Sopuerta). One of the most representative examples of cave burial is found at Pico Ramos. Large quantities of human remains and personal items have been recovered from this small cave.

Indo-European groups first arrived in the Basque Country at the beginning of the First Millennium BC, bringing with them a different, more evolved culture. They spread new funerary rites (cremation) and technological innovations (ironworking and the pottery wheel), establishing settlements on hills and highlands which they protected with stone walls (ring forts or “castros”). They practiced a mixed subsistence economy, which was sometimes insufficient to feed the entire community. With the arrival of Roman troops on the Iberian peninsula and especially with the Cantabrian wars (1st century BC) word of the settlers on the Cantabrian coast spread. Strabo wrote about the way of life of these tribes and for the first time he gave them names. He called the group living between the Ason and Nervion rivers—an area which includes modern-day Muskiz—the Autrigones.

At the beginning of the Christian era, Roman reinforced its colonial policy in the area as the Flaviuses and Antoninuses sought to extend their area of influence to peripheral areas of the empire. In Castro Urdiales they founded the colony of Flaviobriga and probably mined seams of iron in the valley of Somorrostro. When Pliny the Elder spoke of an "iron mountain" in the region of Cantabria in the 1st century AD, he may have been referring to the hills of Triano. The Encartaciones area was also crossed by a major road, which linked Flaviobriga with Pisoraca (Herrera de Pisuerga in Palencia).