Experimentally manipulated water and insect stresses were applied to field-grown corn with different Bacillus thuringiensis (Bt) transgenes and no Bt transgenes, and different non transgenic hybrid backgrounds (2011 and 2012, Corpus Christi, TX). Differences in leaf injury, ear injury, and yield were detected among experimental factors and their interactions. Under high and low water stress, injury from noctuid larvae (Lepidoptera: Noctuidae) on leaves during vegetative growth (primarily from fall armyworm, Spodoptera frugiperda J.E. Smith) and on developing ears (primarily from corn earworm, Helicoverpa zea [Boddie]) was lowest on more recent releases of Bt hybrids (newer Bt hybrids) expressing Cry1A. 105 Cry2Ab2 and Cry 3Bbl, compared with earlier Bt hybrids (older Bt hybrids) expressing CrylAb and Cry3Bbl and non-Bt hybrids. High water stress led to increased leaf injury under substantial fall armyworm feeding pressure in 2011 (as high as 8.7 on a 1–9 scale of increasing injury). In contrast, ear injury by corn earworm (as high as 20 cm² of surface area of injury) was greater in low water stress conditions. Six hybrid backgrounds did not influence leaf injury, while ear injury differences across hybrid backgrounds were detected for non-Bt and older Bt hybrid versions. While newer Bt hybrids expressing Cry1A.105 Cry2Ab2 and Cry 3Bbl had consistent low leaf injury and high yield and low but less consistent ear injury across six hybrid backgrounds, water stress was a key factor that influenced yield. Bt transgenes played a more variable and lesser role when interacting with water stress to affect yield. These results exemplify the interplay of water and insect stress with plant injury and yield, their interactions with Bt transgenes, and the importance of these interactions in considering strategies for Bt transgene use where water stress is common.