A rising global population and demand for protein-rich diets are increasing pressure to maximize agricultural productivity. Rising atmospheric [CO2] is altering global temperature and precipitation patterns, which challenges agricultural productivity. While rising [CO2] provides a unique opportunity to increase the productivity of C3 crops, average yield stimulation observed to date is well below potential gains. Thus, there is room for improving productivity. However, only a fraction of available germplasm of crops has been tested for CO2 responsiveness. Yield is a complex phenotypic trait determined by the interactions of a genotype with the environment. Selection of promising genotypes and characterization of response mechanisms will only be effective if crop improvement and systems biology approaches are closely linked to production environments, that is, on the farm within major growing regions. Free air CO2 enrichment (FACE) experiments can provide the platform upon which to conduct genetic screening and elucidate the inheritance and mechanisms that underlie genotypic differences in productivity under elevated [CO2]. We propose a new generation of large-scale, low-cost per unit area FACE experiments to identify the most CO2-responsive genotypes and provide starting lines for future breeding programmes. This is necessary if we are to realize the potential for yield gains in the future.