Fall armyworm, Spodoptera frugiperda (J.E. Smith) is a polyphagous insect with natural resistance to insecticide; various strategies have been used for its control. Novel compounds derived from N-oxide have low toxicity to humans but are biologically activity against bacteria, fungi, parasites, and even insects. Five N-oxide derivatives (QX1, QX2, QX3, QX4, and QX5) were evaluated through diet and spray assays to determine toxic activity and most-effective administration route in three Mexican populations of S. frugiperda. Larvae were collected from fields of maize, Zea mays L., in three regions of Mexico: Mante, Tamaulipas (Northeast); Durango, Durango (Northwest); and Tapachula, Chiapas (Southern). The three Mexican populations were sensitive to QX5 (benzofuroxan N-oxide derivative) that when ingested killed 100% of larvae, and had variable sensitivity to quinoxaline 1,4-di-N-oxide derivatives that negatively affected growth of larvae. Ingested QX2, QX3, and QX4 most inhibited growth (54–64%) of the Mante population. QX3 most inhibited growth (almost 90%) of the Tapachula population, and Q1 inhibited growth of 91% of the larvae in the Durango population. With topical application, all compounds killed less than 10% of the larvae, and only QX2 and QX3 inhibited growth of 31% of fall armyworm larvae from the Durango population. Benzofuroxane killed most and quinoxalines caused variation in growth inhibition of fall armyworm larvae; in both cases, ingestion was most effective in killing larvae. The benzofuroxan N-oxide derivative might have good potential for development of safer and more effective insecticides against this pest.