Large-scale studies at the regional, national and global scales are increasingly needed to assess nutrient flows in agroecoystems and to identify their drivers. In this study, we aimed to quantify the extent to which regional phosphorus (P) flows and soil P budget depend on agricultural production systems. Phosphorus was taken as a case study due to its sorbing properties in soil and to the many questions concerning its future availability. The issue was studied from two different stages: (1) for the 21 administrative regions of France; and (2) by selecting four contrasting French regions—the Centre region (a crop farming region), Brittany (an animal farming region) and Lorraine and Aquitaine (mixed farming regions). Phosphorus flows and soil P budgets were quantified on a yearly basis for the 21 regions from 1990 to 2006, whereas a 5-year average was calculated for the years 2002–2006 to compare the four selected regions. At the beginning of the study (1990), the calculated P budget was positive for all regions averaging 17.5 kg P ha−1 year−1 which declined over years to 4.4 kg P ha−1 year−1 in 2006, but huge differences between the 21 regions were observed, confirming the heterogeneity of the regional P flows. Agricultural production systems strongly influenced the P flows through feed, fodder and animal excretion, while P fertiliser consumption was only partially influenced. As a consequence, both the regional soil P budgets and the magnitude of soil P inflows and outflows were strongly dependent on the regional agricultural production systems. A balanced soil P budget could be obtained in crop farming regions, but it strongly relied on P fertiliser use. The animal farming regions continued to accumulate P in the soil, and further use of P fertilisers in these regions is questionable. Finally, there was no simple rule between the mixed farming systems and the soil P budget. This study offers some initial elements for understanding the drivers of mineral P fertiliser use, i.e. the factors governing P fertiliser use by the farmers. It may also contribute to the redesign of regional farming systems oriented towards more effective use of nutrients at the global scale.