The elevation of atmospheric CO2 leads to a decline in the plant mineral content, which poses a major threat to food security in the coming decades. To date, very few genes have been identified as having a role in the negative effect of elevated CO2 on plant mineral composition. Yet, several studies have shown a certain degree of diversity in the ionome's response to elevated CO2, associated with genotypic variation. This suggests the existence of genetic factors controlling the effect of CO2 on ionome composition. However, no large-scale studies have been carried out to date to explore the genetic diversity of the ionome responses to elevated CO2. Here, we used six hundred Arabidopsis thaliana accessions, representing geographical distributions ranging from worldwide to regional and local environments, to analyze the natural genetic variation underlying the negative effect of elevated CO2 on the ionome composition in plants. We show that the growth under elevated CO2 leads to a global and important decrease of the ionome content whatever the geographic distribution of the population. We also observed a high range of genetic diversity in the response of the ionome composition to elevated CO2, and we identified sub-populations, showing effects on their ionome ranging from the most pronounced to resilience or even to a benefit in response to elevated CO2. Using genome-wide association mapping on the response of each mineral element to elevated CO2 or on integrative traits, we identified a large set of QTLs and genes associated with the ionome response to elevated CO2. Finally, we demonstrate that manipulating the function of one of these genes can mitigate the negative effect of elevated CO2 on the plant mineral composition. Therefore, this resource will contribute to understand the genetic mechanisms underlying the negative effect of elevated CO2 on the mineral composition of plants, and to the development of biofortified crops adapted to a high-CO2 world.