Pesticide contamination is commonly found as a mixture of different pesticides rather than individual compounds. However, the regulatory risk evaluation is mostly based on the effects of individual pesticides. In the present study, we aimed to investigate the individual and combined toxicities of cypermethrin (CYP) with emamectin benzoate (EMB) and imidacloprid (IMI) to crayfish using acute indices and various sub-lethal endpoints. Semi-static bioassay procedures were followed in the experiment. The 24, 48, and 72 h LC50 values (with 95% confidence limits) of CYP for crayfish were calculated as 0.141, 0.137, and 0.135 ug/ml, respectively, which were higher than those of IMI (75.813, 72.345, 70.568 g/ml) and EMB (34.581, 27.930, 22.298 ug/ml). Pesticide mixtures of CYP and EMB displayed a synergistic response to crayfish; the LC50 was 0.053, 0.050, and 0.048 ug/ml, which was lower than when only CYP was present. Pesticide mixtures of CYP and EMB were found to be highly toxic to crayfish. At the physiological level, both individuals and mixtures of pesticides caused severe injury to the internal organs of crayfish. Taken together, the synergistic effects indicated that it was highly important to include joint toxicity studies when assessing the risk of pesticides.