We evaluated the influences of CO2[Control, ∼ 370 µmol mol−1; 200 µmol mol−1 above ambient applied by free-air CO2 enrichment (FACE)] and soil water (Wet, Dry) on above- and below-ground responses of C3 (cotton, Gossypium hirsutum) and C4 (sorghum, Sorghum bicolor) plants in monocultures and two density mixtures. In monocultures, CO2 enrichment increased height, leaf area, above-ground biomass and reproductive output of cotton, but not sorghum, and was independent of soil water treatment. In mixtures, cotton, but not sorghum, above-ground biomass and height were generally reduced compared to monocultures, across both CO2 and soil water treatments. Density did not affect individual plant responses of either cotton or sorghum across the other treatments. Total (cotton + sorghum) leaf area and above-ground biomass in low-density mixtures were similar between CO2 treatments, but increased by 17–21% with FACE in high-density mixtures, due to a 121% enhancement of cotton leaf area and a 276% increase in biomass under the FACE treatment. Total root biomass in the upper 1.2 m of the soil was not influenced by CO2 or by soil water in monoculture or mixtures; however, under dry conditions we observed significantly more roots at lower soil depths (> 45 cm). Sorghum roots comprised 81–85% of the total roots in the low-density mixture and 58–73% in the high-density mixture. CO2-enrichment partly offset negative effects of interspecific competition on cotton in both low- and high-density mixtures by increasing above-ground biomass, with a greater relative increase in the high-density mixture. As a consequence, CO2-enrichment increased total above-ground yield of the mixture at high density. Individual plant responses to CO2 enrichment in global change models that evaluate mixed plant communities should be adjusted to incorporate feedbacks for interspecific competition. Future field studies in natural ecosystems should address the role that a CO2-mediated increase in C3 growth may have on subsequent vegetation change.