Neonicotinoid insecticides are the most widely used class of insecticides worldwide. Concern has grown over their widespread environmental presence and potential unintended adverse effects. The present study examined hydrolysis and photolysis reaction rates of neonicotinoids and assessed any residual toxicity of reaction products. Hydrolysis rates were tested between pH 4 and 10 and found to be base‐catalyzed. Experiments revealed a nonelementary rate law for hydrolysis, with the hydroxide concentration raised to a power of 0.55 ± 0.09, which has implications for accurate prediction of environmental half‐lives. Divalent metal ions (Cu2+, Ni2+, Zn2+) and minerals (kaolinite, goethite, TiO2) had no effect on hydrolysis rates. The hydrolysis rate in a natural water, however, was slower than that predicted by buffered experiments. Nitenpyram, imidacloprid, thiamethoxam, and clothianidin reacted via direct photolysis in both ultrapure and natural waters, with average quantum yields of 0.024 ± 0.001, 0.0105 ± 0.0002, 0.0140 ± 0.0002, and 0.0101 ± 0.0001, respectively. Acetamiprid primarily underwent indirect photolysis by reaction with OH· (1.7 ± [0.2] × 109 M−1 s−1). For all compounds, the urea derivative was the most commonly detected product in both hydrolysis and photolysis experiments. Using mosquito (Culex pipiens) larvae, no residual toxicity of reaction products was observed. Results indicate long environmental half‐lives for the tested neonicotinoids, which may help to explain their ubiquitous presence in environmental matrices. Environ Toxicol Chem 2018;37:2797–2809. © 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC