Spodoptera frugiperda (fall armyworm, FAW) is one of the most devastating insect pests to corn and soybean production in the Americas and is rapidly expanding its range worldwide. It is known to be hard to control either by chemical insecticide applications or by GM. Although the use of GM traits can be an effective way to control this pest, it is very rare to find native insecticidal proteins that provide the necessary level of FAW control in crop fields where FAW pressure and damage are high. Insecticidal Cry proteins sourced from Bacillus thuringiensis have been heavily utilized in the development of crops with GM traits; however, it is increasingly difficult to identify Cry proteins with unique modes of action. Protein engineering via a phylogenetically guided Cry protein domain swapping approach enabled us to discover novel chimeric Cry proteins engineered from inactive parent sequences. Some of these chimeras show excellent efficacy against key biotypes of FAW from Brazil and North America. In this study, we characterized a Cry-based chimera eCry1Gb.1Ig that is a very potent FAW toxin. eCry1Gb.1Ig showed high efficacy against multiple FAW strains that are resistant to various traits, including Cry1Fa, Vip3Aa and Cry1A.105/Cry2Ab. These results clearly indicate that the FAW strains resistant to Cry1Fa, Vip3Aa or Cry1A.105/Cry2Ab demonstrate no cross-resistance to eCry1Gb.1Ig and strongly suggest that eCry1Gb.1Ig acts through a novel mode of action compared to the existing traits. In addition to its FAW activity, eCry1Gb.1Ig has also been shown to control Chrysodeixis includens (soybean looper, SBL) and Anticarsia gemmatalis (velvetbean caterpillar, VBC), which are significant pests of soybean. When eCry1Gb.1Ig was introduced into corn and soybean crops, transgenic events showed strong efficacy against FAW, SBL and VBC, but no adverse plant phenotypes. This suggests that the in planta expression of the eCry1Gb.1Ig protein does not compromise plant growth or reproduction and can protect plants from FAW-related damage. Therefore, this valuable discovery will provide a differentiating FAW control trait that will give growers another tool to help them reduce yield loss due to FAW.