Following the emergence of Melanaphis sorghi (Theobald) (Hemiptera: Aphididae) as a new pest of sorghum in the United States, research was conducted to identify tools and techniques successful at reducing populations and preventing economic losses in grain sorghum, Sorghum bicolor (L.) Moench. The objective of this study was to assess the efficacy of seed- and foliar-applied insecticide treatments for management of M. sorghi. Small plot experiments were replicated at two locations to evaluate residual activity of neonicotinoid seed treatments and foliar insecticides. Natural enemy presence was recorded in each of these trials to determine which predator and parasitoid species were using M. sorghi as prey. All seed treatments suppressed M. sorghi populations below a treatment threshold of 75 aphids per plant for 30% of plants for >6 weeks after planting. Foliar insecticides including flupyradifurone, sulfoxaflor, and thiamethoxam provided 3–4 weeks of population suppression, irrespective of M. sorghi pressure. Fifteen natural enemy species were identified in this study, and community structure varied temporally and geographically. In general, natural enemy species richness was correlated with aphid abundance. We identified the most efficacious insecticides available for management of M. sorghi and determined that they should be compatible with biological control and integrated pest management programs.