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.