Cotton aphid, Aphis gossypii Glover, has a history of developing resistance to novel insecticides. A program is needed to monitor cotton aphid susceptibility to new insecticides. Concentration-mortality bioassays were conducted from 2008 to 2011 to monitor the susceptibility of cotton aphids from fields across the midsouthern United States to thiamethoxam and sulfoxaflor. Flonicamid was included in 2010 and 2011. Bioassays followed the procedures described by the Insecticide Resistance Action Committee for testing neonicotinoids against cotton aphid. Mortality was rated at 48 and 72 h. These bioassays suggest that high levels of resistance to thiamethoxam occur in cotton aphid throughout the midsouthern United States. Resistance ratios ranged from 0.9 to 562.6 at 48 h, and from 0.9 to 29.1 at 72 h. Aphid colonies tested were considered susceptible to flonicamid and sulfoxaflor. The LC₅₀ values ranged from 1.43 to 6.60 ppm for flonicamid. The LC₅₀ values for sulfoxaflor ranged from 1.01 to 5.85 ppm and 0.92–4.13 ppm at 48 and 72 h, respectively. These values represent the baseline variability of the susceptibility of cotton aphid to flonicamid and sulfoxaflor. The moderate level of variability observed combined with the high level of efficacy at low rates and the high reproductive rate of cotton aphid suggests that an effective resistance management plan needs to be devised for these insecticides. Flonicamid and sulfoxaflor should provide effective control of cotton aphid in areas where thiamethoxam resistance occurs. However, these insecticides need to be incorporated into a rotation strategy to preserve their efficacy against cotton aphid.