The pyramided genetically modified (GM) soybean [Glycine max L. (Merr.)] MON87751 × MON87708 × MON87701 × MON89788, expressing Cry1A.105, Cry2Ab2, and Cry1Ac from Bacillus thuringiensis Berliner, was approved for commercial use in Brazil. We conducted laboratory, greenhouse, and field studies to assess the efficacy of this Bt soybean against key soybean lepidopteran pests. Neonates of Anticarsia gemmatalis (Hübner) (Lepidoptera: Erebidae), Chrysodeixis includens (Walker), and Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) were exposed to Bt proteins in diet-overlay bioassays. MON87751 × MON87708 × MON87701 × MON89788 soybean and individual components were evaluated in laboratory (leaf disc), greenhouse (high artificial infestations), and in field conditions (natural infestations). Neonates of A. gemmatalis, C. includens, and H. armigera were highly susceptible to Cry1A.105 (LC50 from 0.79 to 48.22 ng/cm2), Cry2Ab2 (LC50 from 1.24 to 8.36 ng/cm2), and Cry1Ac (LC50 from 0.15 to 5.07 ng/cm2) in diet-overlay bioassays. In laboratory leaf disc bioassays and greenhouse trials, MON87751 × MON87708 × MON87701 × MON89788 soybean as well as the individual components were highly effective in controlling A. gemmatalis, C. includens, and H. armigera. Similarly, under field conditions, the pyramided genotypes expressing Cry1A.105, Cry2Ab2, and Cry1Ac were highly effective at protecting soybean against C. includens. We concluded that the individual Bt proteins expressed by GM soybean MON87751 × MON87708 × MON87701 × MON89788 killed all or nearly all the susceptible A. gemmatalis, C. includens, and H. armigera, fulfilling one important criterion for successfully delaying resistance to pyramided Bt crops.