Recently, successful predictions using machine learning (ML) algorithms have been reported in various fields. However, in traumatic brain injury (TBI) cohorts, few studies have examined modern ML algorithms. To develop a simple ML model for TBI outcome prediction, we conducted a performance comparison of nine algorithms: ridge regression, LASSO regression, random forest, gradient boosting, extra trees, decision tree, Gaussian naïve Bayes, multinomial naïve Bayes, and support vector machine. Fourteen feasible parameters were introduced in the ML models, including age, Glasgow coma scale, systolic blood pressure, abnormal pupillary response, major extracranial injury, computed tomography findings, and routinely collected laboratory values (glucose, C-reactive protein, and fibrin/fibrinogen degradation products). Data from 232 TBI patients were randomly divided into a training sample (80%) for hyperparameter tuning and validation sample (20%). The bootstrap method was used for validation. Random forest demonstrated the best performance for in-hospital poor outcome prediction and ridge regression for in-hospital mortality prediction: the mean statistical measures were 100% sensitivity, 72.3% specificity, 91.7% accuracy, and 0.895 area under the receiver operating characteristic curve (AUC); and 88.4% sensitivity, 88.2% specificity, 88.6% accuracy, and 0.875 AUC, respectively. Based on the feature selection method using the tree-based ensemble algorithm, age, Glasgow coma scale, fibrin/fibrinogen degradation products, and glucose were identified as the most important prognostic factors for poor outcome and mortality. Our results indicated the relatively good predictive performance of modern ML for TBI outcome. Further external validation is required for more heterogeneous samples to confirm our results.