Frequent inspections on sorghum and maize crops during seasons of 2021 and 2022 in some regions in Bani-Suef governorate, Egypt, discovered unprecedented invasions of Spodoptera frugiperda(J. E. Smith). Accordingly, our study on Beauveria bassianaand spinetoram was supporter to the Food and Agriculture Organization’s tendency in adopting biorational insecticides against S. frugiperdain Egypt.Exposure toxicity of LC25values at 48 h of B. bassianawere 2.7 × 106and 5.2 × 106conidia mL−1and spinetoram were 0.019 and 0.048 mg L−1against the 2nd and 4th instar larvae laboratory strain of S. frugiperda, respectively. Sub-lethal effects (LC25) were accomplished on biological parameters against both instar larvae. LC25of B. bassianareduced adult emergency (89.91 and 91.05%) more than spinetoram (75.99 and 79.49%) against the 2nd and 4th instar larvae, respectively. The 2nd instar larvae exposed to LC25of B. bassianasuppressed female fecundity (0.00 eggs) more than spinetoram (19.74 eggs). Enzymatic activity of lipase in hemolymph, fat bodies, and mid-gut of the 4th instars at 48 h showed significant drop in B. bassianamore than spinetoram. Glutathione-S-transferase (GST) levels in hemolymph for both insecticides were equal and exceeded the control. Fat bodies and mid-gut possessed the highest GST activity in B. bassianafollowed by spinetoram and the control. Residual efficacy of spinetoram exceled B. bassianaat their field rates under semi-field condition in Bani-Suef along the two seasons of maize crop against both instars. Eventually, B. bassianaalongside spinetoram could afford good control especially on early instar larvae of S. frugiperda.