The performance of a plate heat exchanger (PHE) using water as the working fluid with zigzag flow channels was optimized in the present study. The optimal operating conditions of the PHE are explored experimentally by the Taguchi method, with effectiveness as the objective function. The results are further verified by the analysis of variance (ANOVA). In addition, the zigzag flow channel geometry is optimized by the non-dominated sorting genetic algorithm-II (NSGA-II), in which the effectiveness and pressure drop of the PHE are considered the two objective functions in the multi-objective optimization process. The experimental results show that the ratio of flow rates is the most important factor affecting the effectiveness of the PHE. The optimal operating conditions are the temperatures of 95 °C and 10 °C at the inlets of hot and cold water flows, respectively, with a cold/hot flow rate ratio of 0.25. The resultant effectiveness is 0.945. Three geometric parameters of the zigzag flow channel are considered, including the entrance length, the bending angle, and the fillet radius. The sensitivity analysis of the parameters reveals that a conflict exists between the two objective functions, and multi-objective optimization is necessary for the zigzag flow channel geometry. The numerical simulations successfully obtain the Pareto optimal front for the two objective functions, which benefits the determination of the geometric design for the zigzag flow channel.