The toxicity of single and combined mixtures of 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP), and pentachlorophenol (PCP) to Daphnia magna was studied. The toxicity ranking of these three single chlorophenols (CPs) to Daphnia magna was PCP > 2,4-DCP > 2,4,6-TCP. The toxic units (TU) approach was used to estimate the combined effects in experiments, the median effective concentration (EC50) values were 0.87–1.21 and 0.46–0.59 for binary and ternary mixtures, respectively. Response surface models of General Linear Models (R2 > 0.90, residual deviation < 3.25) were established for all three binary mixtures. The toxicity for ternary mixtures based on the EC50-value and 10% effective concentration (EC10)-value fixed mixture ratio presented a synergism. The risk based on the single CP’s toxicity test may be underestimated. In addition, four approaches (concentration addition, toxicity equivalency factors, effect summation, and independent action) were used for the calculation of combined effects of the mixture. The experimental results showed that concentration addition and toxicity equivalency factor approaches were effective methods for calculation of additive effects of mixtures from binary systems of CPs; while independent action and effect summation (low simulated tail) predicted lower toxicity than experimental results. Limitations of the traditional focus on the effects of single agents were highlighted; hazard assessments ignoring the possibility of joint action of CPs will almost certainly lead to significant underestimations of risk.