Climate changes and human activities have impacted the Mediterranean ecosystem for thousands of years, but the available quantitative evidence is incomplete, hindering a detailed assessment of the marine ecosystem's baseline state and resources. To disentangle these impacts, we investigated changes in the distribution, abundance and body size of commercially important species of marine mammals, fishes, and molluscs over the last 130,000 (130 ka) years until the Industrial Revolution (1850) in three Mediterranean sub-regions: Western, Eastern and Adriatic. We identified and integrated quantitative data available from the literature on two marine mammals, thirteen fish and three molluscs, revealing consistent and significant climatic and anthropogenic impacts on three species: the banded-dye murex, the Atlantic bluefin tuna and the gilthead sea bream. Climate change, particularly temperature changes, was the most important factor influencing the past abundance and body size of Atlantic bluefin tuna, while sub-regional differences in the stable isotopic composition of archaeological skeletal remains reflected shifts in the system's productivity. Human activities, particularly overexploitation, impacted the abundance of both banded-dye murex and Atlantic bluefin tuna, as well as the body size of gilthead sea bream and Atlantic bluefin tuna. Our results highlight the significance of studying the relationships between climate, human activities, and marine resources in this large marine ecosystem before the Industrial Revolution and showcases the relevance of integrating past quantitative data with contemporary data to reconstruct ecological baselines and obtain longer and more comprehensive time series of ecosystem change.