The operational costs of the advanced Air Traffic Management (ATM) solutions are often prohibitive in low- and medium-sized airports. Therefore, new and complementary solutions are currently under research in order to take advantage of existing infrastructure and offer low-cost alternatives. The 5G signals are particularly attractive in an ATM context due to their promising potential in wireless positioning and sensing via Time-of-Arrival (ToA) and Angle-of-Arrival (AoA) algorithms. However, ToA and AoA methods are known to be highly sensitive to the presence of multipath and Non-Line-of-Sight (NLOS) scenarios. Yet, LOS detection in the context of 5G signals has been poorly addressed in the literature so far, to the best of the Authors’ knowledge. This paper focuses on LOS/NLOS detection methods for 5G signals by using both statistical/model-driven and data-driven/machine learning (ML) approaches and three challenging channel model classes widely used in 5G: namely Tapped Delay Line (TDL), Clustered Delay Line (CDL) and Winner II channel models. We show that, with simulated data, the ML-based detection can reach between 80% and 98% detection accuracy for TDL, CDL and Winner II channel models and that TDL is the most challenging in terms of LOS detection capabilities, as its richness of features is the lowest compared to CDL and Winner II channels. We also validate the findings through in-lab measurements with 5G signals and Yagi and 3D-vector antenna and show that measurement-based detection probabilities can reach 99–100% with a sufficient amount of training data and XGBoost or Random Forest classifiers.