The management and operation of the wastewater treatment plants (WWTP) have an important role in the controlling and monitoring of the plants' operations. Various performance data are taken into account in the controlling of the WWTP. The irregularities between operating parameters often lead to management problems that cannot be overcome. The aim of this study is to provide a simple and reliable prediction model to estimate the biochemical oxygen demand (BOD) with specific water quality parameters like wastewater temperature, pH, chemical oxygen demand, suspended sediment, total nitrogen, total phosphorus, electrical conductivity, and input discharge. The data records in this study were measured between June 2015 and May 2016 and obtained from the laboratory of Antalya Hurma WWTP. In the creation of the model, classical regression analysis, multivariate adaptive regression splines (MARS), artificial bee colony, and teaching-learning based optimization were used. The root mean square error and the mean absolute error were used to evaluate performance criteria for each model. When the results of the analyses were compared with each other, it was observed that the MARS method gave better estimation results than the other methods used in the study. As a result, it was evinced that the MARS method produces acceptable results in the BOD estimation.