Increasing surface UV-B radiation (UV-B) and atmospheric carbon dioxide concentration [(CO2)] are two major issues of climate change and agriculture. Although numerous studies have evaluated elevated UV-B or (CO2) effects on crop growth, development and yield, little is known about the interactive effects of these two factors on cotton. The objective of this study was to determine the combined effects of elevated (CO2) and UV-B radiation on cotton growth and physiology under controlled environmental conditions. The four treatments imposed were control [360 μmol (CO2) mol-1 and 8 kJ m-2 d-1 UV-B], +CO2 [720 μmol (CO2) mol-1 and 8 kJ m-2 d-1 UV-B], +UV-B [360 μmol (CO2) mol-1 and 16 kJ m-2 d-1 UV-B] and +CO2+UV-B [720 μmol (CO2) mol-1 and 16 kJ m-2 d-1 UV-B]. Treatments were imposed from emergence through three weeks after the first flower stage. Plants grown in +CO2 showed greater plant height, leaf thickness, leaf area, leaf and canopy photosynthesis (PN) and total biomass compared to the control, and fruit biomass was not affected by +CO2 conditions. On the other hand, plants grown in +UV-B treatment exhibited slower growth as reflected by reduced plant height, shorter internodes and branch lengths, and total biomass due to smaller leaf areas and less lower leaf PN. The +UV-B treatment also altered the leaf morphology and significantly reduced flower and petal lengths and petal area. Reduction in fruit production under both +UV-B and +CO2+UV-B treatments was due to reduced photosynthesis and alterations in reproductive development. The results also showed interactive effects of UV-B on cotton leaf PN, phenolics, wax content and some physiological parameters measured. Thus, a failure to increase cotton fruit production with +CO2 and +CO2+UV-B suggests that breeding UV-B radiation-tolerant cultivars is important in both the present and future solar UV-B radiation environments.