The possible co-variation of human occupation and vegetation from the Middle Neolithic to the beginning of the Iron Age (7.5–2.8 ka BP) in Central Sicily in the context of the central Mediterranean between Middle and Late Holocene are analysed in this paper to provide new insights on Sicilian prehistoric demography. The demographic and economic trends during these millennia were reconstructed using archaeological, Accelerator Mass Spectrometry 14 C dates, palynological, archaeobotanical, and zooarchaeological data from the northern, central, and southern sectors of Central Sicily through a diachronic comparison with variation in Arboreal Pollen, Anthropogenic Pollen Indicators, Olea-Juglans-Castanea pollen, microcharcoals, and Sporormiella from four pollen cores from sites in different ecosystems. A very significant spread of farming activities was found at the end of the Neolithic, together with an apparent demographic gap during the Middle Copper Age, and the emergence of agricultural landscapes at the end of the Copper Age associated with a striking increase in population. A combination of cultural and climatic changes during the late phase of the Bronze Age resulted in a subsequent overall decrease in population.