Interactive effects of multiple environmental stresses are predicted to have a negative effect on cotton growth and development and these effects will be exacerbated in the future climate. The objectives of this study were to test the hypothesis that cotton cultivars differ in their responses to multiple environmental factors of (CO₂) [400 and 750 µmol·mol⁻¹ (+(CO₂)], temperature [28/20 and 20/12°C (−T)], and UV−B radiation [0 and 10 kJ·m⁻²·d⁻¹ (+UV−B)]. A genetic and molecular standard (TM-1) and three modern cotton cultivars (DP1522B2XF, PHY496W3R, and ST4747GLB2) were grown in eight sunlit, controlled environment chambers with control treatment 400 µmol·mol⁻¹ [CO₂], 28/21°C temperature, and 0 kJ UV−B. The results showed significant differences among the cultivars for most of the shoot and root parameters. Plants grown under low temperature alone or as a combination with+UV−B treatment caused more detrimental effects on root and shoot vigor. Although the elevated CO₂ treatments weakened the damaging effects of higher UV−B levels on cotton growth on all cultivars, increased CO₂ could not mask the negative effects of low temperature. When comparing all cultivars, genetic standard TM-1 produced the smallest values for the majority of traits under CO₂, UV−B, and low temperature either alone or in combination with other treatments. Based on principal component analysis, the four cultivars were classified as tolerant (DP1522B2XF), intermediate (PHY496W3R and ST4747GLB2) and sensitive (TM-1) to multiple environmental stresses.Low temperature was identified as the most damaging treatment to cotton early seedling vigor while elevated CO₂ caused the least. Existing variability of cotton cultivars in response to multiple environmental stresses could allow for selection of cultivars with the best coping ability and higher lint yield for future climate change environments.