In this paper, a methodology based on data-driven models is developed to predict the NOx emissions of an internal combustion engine using, as inputs, a set of ECU channels representing the main engine actuations. Several regressors derived from the machine learning and deep learning algorithms are tested and compared in terms of prediction accuracy and computational efficiency to assess the most suitable for the aim of this work. Six Real Driving Emission (RDE) cycles performed at the roll bench were used for the model training, while another two RDE cycles and a steady-state map of NOx emissions were used to test the model under dynamic and stationary conditions, respectively. The models considered include Polynomial Regressor (PR), Support Vector Regressor (SVR), Random Forest Regressor (RF), Light Gradient Boosting Regressor (LightGBR) and Feed-Forward Neural Network (ANN). Ensemble methods such as Random Forest and LightGBR proved to have similar performances in terms of prediction accuracy, with LightGBR requiring a much lower training time. Afterwards, LightGBR predictions are compared with experimental NOx measurements in steady-state conditions and during two RDE cycles. Coefficient of determination (R2), normalized root mean squared error (nRMSE) and mean average percentage error (MAPE) are the main metrics used. The NOx emissions predicted by the LightGBR show good coherence with the experimental test set, both with the steady-state NOx map (R2 = 0.91 and MAPE = 6.42%) and with the RDE cycles (R2 = 0.95 and nRMSE = 0.04).