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The development of high-yielding heat-tolerant cotton cultivars harboring plastic phenotypes across warming climatic regions is prime objectives of today’s cotton breeding programs. We evaluated eight parents and 15 F1 hybrids under normal and heat stress conditions. Agronomic and biochemical characters were analyzed using standard least square, correlation, principal component analysis (PCA), and hierarchical clustering. The results explained a significant reduction in all traits except hydrogen peroxide contents, catalase, and peroxidase activities with a prominent increase under heat stress. A significant positive correlation was observed among all agronomic and biochemical traits. POD was found to have a maximum positive correlation with CAT (0.947) and minimum with boll weight (0.050). PCA showed first two components accounting for 78.64% of the total variation, with 55.83% and 22.80% of the total variation, respectively. Based on multivariate analyses methods 23 genotypes have been placed in 3 groups: tolerant (cluster-3), moderately tolerant (cluster-2), and susceptible (cluster-1). In a general perspective hybrids have better performance across normal and heat stress supports the idea of hybrid adaptability across stress environments. In specific FH-458 × FH-313 cross performed best across both conditions for yield and physiological traits. Hence, the generated information from the present study would support breeders in developing heat-resilient cultivars to endure the prevailing extreme environmental conditions.