The intention of this study was to assess pollutant removal efficiency of the full scale wastewater treatment plant of Walia Brewery by collecting wastewater samples from the influent and outlet of each treatment unit using laboratory method and Simulation of wastewater treatment plant performance using Artificial Neural Networks .The outcomes of the present study was revealed out two main results: laboratory Analysis result and Artificial Neural Network modeled result. The laboratory analysis result showed that except for temperature, all of the other analyzed parameters of raw wastewater exceeded the national discharge limit. In most cases, the values decreased as the wastewater passed over the treatment units of the plant indicating an involvement of the units in the removal of pollutants. The brewery‟s treated final effluent had a mean value and standard deviation of 7.62+0.13(pH), 23.8+1.93(T), 228.6+10.16(EC), 228.84+8.68(COD), and 16+2.91(NH3 -N) which were within national industrial wastewater discharge limits. However, the values of some parameters namely 90.84+44.09(BOD), 51.04+12.30(TSS), 40.2+6.45(TN), 29.02+3.38(TP) and 11.36+3.41(NO3-N) were higher than the limits. The overall pollutant removal efficiency of the treatment plant was 92.43 %( BOD), 89.77 %( COD), 92.05%(TSS), 35.16%(TN), 19.38%(TP), 49.36%(NH3_N) and 54.92%(NO3_N). The Artificial neural network modelling result revealed that the Multi-layer Perception performance model was better than the multiply liner regression model. It was found that the artificial neural network multi-layer perception model could be modeled success fully in estimating the common effluents (BOD, COD and TSS) in the outlet of walia brewery wastewater treatment plant. Finally, study was suggested the recommendation for Walia brewery wastewater treatment plant. Therefore, in order to make the treatment plant more efficiency, high control response and meet standard discharge limits set by Ethiopian Environment protection authority for industry effluent (2003), the factory should take some technology, technical and recycling measures.