This study compared two neural network models (Multilayer Perceptron and Generalized Regression Neural Network) with a view to identifying the best model for predicting students’ academic performance based on single performance factor. Only academic factor (students’ results) was considered as the single performance factor of the study. One cohort of graduated students’ academic data was collected from the Computer Science and Engineering Department of Obafemi Awolowo University, Nigeria using documents and records technique. The models were simulated using MATLAB version 2015a and evaluated using mean square error, receiver operating characteristics and accuracy as the performance metrics. The results obtained show that although Multilayer Perceptron had prediction accuracy of 75%, Generalized Regression Neural Network had a better accuracy. The response time of Generalized Regression Neural Network (0.016sec) was faster than Multilayer Perceptron (0.03sec) and its memory consumption size (5kb) lower than that of Multilayer Perceptron (8kb). The simulated models were further compared with t-test method using a confidence interval of 95%. The attained t-test result from p-value (0.6854) suggests acceptance of null hypothesis, which shows that there is no significant difference between the predicted Grade Point Average and the actual Grade Point Average. The findings therefore reveal that the overall performance of Generalized Regression Neural Network outperforms the Multilayer Perceptron model with an accuracy of 95%. The study concluded that Generalized Regression Neural Network model which was simulated and with 95 % accuracy could be deployed by educationists to predict students’ academic performance using single performance factor.