Turbulent fluctuations of the atmospheric refraction index, so-called optical turbulence, can significantly distort propagating laser beams. Therefore, modeling the strength of these fluctuations (C n 2) is highly relevant for the successful development and deployment of future free-space optical communication links. In this Letter, we propose a physics-informed machine learning (ML) methodology, Π-ML, based on dimensional analysis and gradient boosting to estimate C n 2. Through a systematic feature importance analysis, we identify the normalized variance of potential temperature as the dominating feature for predicting C n 2. For statistical robustness, we train an ensemble of models which yields high performance on the out-of-sample data of R2 = 0.958 ± 0.001.