This study aimed to analyze the combined impact of CO2 and drought stress at the flowering stage on carbon (C), nitrogen (N), and CN ratios in leaves, stem, and grains of bread wheat. Six diverse bread wheat genotypes, comprised of two commercial checks, two landraces, and two synthetics derivatives, were grown at two levels of CO2, i.e., 400 ppm and 800 ppm, and drought stress was imposed at the flowering stage through progressive soil drying. Stem, leaf, and grain samples were taken at maturity and concentrations of C and N were determined. Our results indicate that the threshold value of fraction of transpirable soil water (CFTSW) at which it diverges towards closure of stomata was different among genotypes and a higher range of values was estimated under elevated CO2. Drought significantly increased C levels in leaves and N levels in grains but decreased N levels in leaves, which increased CN ratios in leaves. In contrast, drought significantly reduced CN ratios in grains. Genotypes differed significantly in N content in grains, where the landrace derivative L2 maintained the highest N content. Moreover, pronounced changes in leaf N and CN ratios were induced by the combination of elevated CO2 and drought stress. Additionally, combined correlation and biplot analyses indicate a strong positive association of grain CN (GCN) with grain number, weight, and grain yield. These effects possibly interact with drought to strongly interfere with the impact of elevated CO2. The differential performance of the tested genotypes shows that selection of appropriate germplasm is essential to maintain agricultural production.