When a domestic wastewater treatment plant (DWWTP) is put into operation, variations of the wastewater quantity and quality must be predicted using mathematical models to assist in operating the wastewater treatment plant such that the treated effluent will be controlled and meet discharge standards. In this study, three types of gray model (GM) including GM (1, N), GM (1, 1), and rolling GM (1, 1) were used to predict the effluent biochemical oxygen demand (BOD), chemical oxygen demand (COD), and suspended solids (SS) from the DWWTP of conventional activated sludge process. The predicted results were compared with those obtained using backpropagation neural network (BPNN). The simulation results indicated that the minimum mean absolute percentage errors of 43.79%, 16.21%, and 30.11% for BOD, COD, and SS could be achieved. The fitness was higher when using BPNN for prediction of BOD (34.77%), but it required a large quantity of data for constructing model. Contrarily, GM only required a small amount of data (at least four data) and the prediction results were analogous to those of BPNN, even lower than that of BPNN when predicting COD (16.21%) and SS (30.11%). According to the prediction, results suggested that GM could predict the domestic effluent variation when its effluent data were insufficient.