Insecticidal efficacy of neonicotinoid insecticides used against tobacco thrips, Frankliniella fusca (Hinds) (Thysanoptera: Thripidae), in cotton, Gossypium hirisutum L. (Malvales: Malvaceae), was evaluated for field populations collected in Mississippi during 2014–2016. Resistance was documented in 16 and 57% of populations to imidacloprid and thiamethoxam, respectively. Resistance levels did not vary by host plant for any neonicotinoid, but resistance levels varied between the two main agricultural areas (Delta and Hills) of Mississippi and among years for some neonicotinoids. In spite of documented resistance, neonicotinoid seed treatments are still used on cotton in the midsouthern United States due to the lack of reliable alternative management strategies. The development of alternative thrips management strategies is critical to the sustainability of cotton production in the midsouthern United States.