Monitoring insect responses to crops genetically engineered to produce insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) for the past 25 years has provided valuable lessons. Abundant refuges of non-Bt host plants can delay evolution of pest resistance, even when inheritance of resistance is not recessive. Also, Bt crops producing multiple Bt toxins are especially advantageous against pest populations that are susceptible to each of the toxins. Bt maize may be useful for addressing the recent invasion of Africa by fall armyworm (FAW), Spodoptera frugiperda, a lepidopteran pest of maize and other crops. In the Americas, however, FAW rapidly evolved practical resistance to maize producing one Bt toxin (Cry1Ab or Cry1Fa). Aside from South Africa, Bt maize has not been approved for cultivation in Africa, where stakeholders in each nation will make decisions about its deployment. We recommend mandated refuges of non-Bt maize or other non-Bt host plants of at least 50% of total maize hectares for single-toxin Bt maize and 20% for Bt maize producing two or more distinct toxins that are each highly effective against FAW. The smallholder practices of planting more than one maize cultivar and intercropping maize with other FAW host plants could facilitate compliance. We also propose creating and providing smallholder farmers access to Bt maize that produces four distinct Bt toxins encoded by linked genes in a single transgene cassette. Using this novel Bt maize as one component of integrated pest management could sustainably improve control of lepidopteran pests including FAW.