A methodology has been developed to quantify the economic value of the provisioning ecosystem services in the South-West of Europe (SUDOE) at any scale. This article describes the methodology that allows the quantification of nutritional and non-nutritional materials and their economic valuation related to agriculture activities at the regional scale. In a complementary way, quantification and valuation of freshwater consumption for domestic uses is described using regional official statistics converted into basin statistics by a geographical scale change matrix. The results show important differences depending on the regions at a sub-system scale. The highest values of agricultural production and its economic valuation are observed in the southeastern part of the SUDOE territory (South France, Spain, and Portugal), both in absolute and relative terms. In the Tagus basin, where the two capitals (Madrid and Lisbon) are located, the water supply and economic value are the highest in the SUDOE region. Provisioning ES is valued at 56.7 billion euros in SUDOE territory per year (current 2015 euros). In conclusion, this work makes it possible to identify those systems with higher economic valuation of provisioning ecosystem services, which, together with the expected increase in temperature and decrease/irregular rainfall, makes these areas particularly vulnerable. The proposed methodology can be applied to any river basin in the world. Graphical Abstract