The marsh ramshorn snail, Planorbella trivolvis, is an intermediate host of trematodes such as Bolbophorus damnificus, a pathogen of channel catfish (Ictalurus punctatus). To reduce economic losses during catfish aquaculture operations, methods are being sought to interrupt the B. damnificus life cycle by reducing marsh ramshorn snail populations in aquaculture ponds. Copper (Cu) is an effective molluscicide used to treat snails. While Cu toxicity is influenced by water quality parameters, such as hardness, pH, alkalinity, and dissolved organic matter, our understanding of the influence of these water quality parameters on Cu toxicity to P. trivolvis is limited. This study aims to investigate the impact of hardness, pH, and dissolved organic carbon (DOC) on Cu toxicity to P. trivolvis, and to develop multiple linear regression models to predict Cu toxicity to P. trivolvis based on water quality parameters. The standard 96-h toxicity test was used to determine the toxicity of Cu to the snail. Results showed that hardness, pH, and DOC strongly influenced Cu toxicity to laboratory-cultured snails. The 96-h LC50 increased from 12 µg/L Cu to 41 µg/L Cu when hardness was increased from 40 to 165 mg/L as CaCO3. Increasing pH from 6.2 to 8.1 also increased 96-h LC50 from 4 µg/L to 14 µg/L Cu. The 96-h LC50 increased from 23 to 105 µg/L Cu when DOC was increased from 0 to 20 mg/L. The 96-h LC50 was a function of pH, hardness, and DOC. The model prediction explained ~80% of the experimental data. The model can be used to calculate appropriate Cu doses for treating P. trivolvis to minimize Cu load into aquaculture pond systems and reduce treatment costs for commercial catfish producers.