“‘latex Machine learning (ML) models are valuable research tools for making accurate predictions. However, ML models often unreliably extrapolate outside their training data. We propose an uncertainty quantification method for ML models (and generally for other nonlinear models) with parameters trained by least squares regression. The uncertainty measure is based on the multiparameter delta method from statistics, which gives the standard error of the prediction. The uncertainty measure requires the gradient of the model prediction and the Hessian of the loss function, both with respect to model parameters. Both the gradient and Hessian can be readily obtained from most ML software frameworks by automatic differentiation. We show that the uncertainty measure is larger for input space regions that are not part of the training data. Therefore this method can be used to identify extrapolation and to aid in selecting training data or assessing model reliability.