Combined application of nitrogen (N), phosphorus (P), and potassium (K) is a valuable practice to improve the growth and physiological activities of cotton, especially during a boll setting. The main purpose of this research was to investigate the effects of the different combined ratios of nitrogen (N), phosphorus (P), and K (potassium) on morpho-physiological activities of Bacillus thuringiensis (Bt) cotton genotypes Siza 1 and Sikang 1 during the cotton boll development stage. A two-year (2016–2017) field experiment was performed in which the total amount of combined N, P, and K were applied at different levels, B1 = 150 N, 0 P2O5, and 0 K2O kg ha−1 (control), B2 = 150 N, 45 P2O5, and 90 K2O kg ha−1, B3 = 150 N, 90 P2O5, and 135 K2O kg ha−1, and B4 = 150 N, 135 P2O5, and 180 K2O kg ha−1. Results revealed that combined application of N, P, and K significantly increased boll length by 5.8% and 2.3%, fresh boll weight by 12.2% and 16.4%, dry lint weight by 15.2% and 1.7%, number of seeds boll−1 by 15.2% and 2.5% as well as dry boll shell weight by 11.0% and 4.9% as compared with the treatment without P and K (1:0:0) across two growing seasons. Furthermore, superoxide dismutase activity was improved by 2.3% and 15.6% and soluble protein by 5.1% and 14.1% as compared with the control, respectively. Our study indicated that combined application of N, P, and K at appropriate ratios enhanced morpho-physiological activities (boll length, boll width, boll weight, protein content, sugar content, and superoxide dismutase) of cotton during boll development and generally the ratio of 150:135:180 considerably performed best amongst all treatments during two growing seasons in this study.