Piles are common support elements for marine and coastal structures. The scour around pile foundations caused by currents is a major threat to the stability and safety of these structures. The empirical equations commonly used for estimating the equilibrium scour depth around pile groups are limited in their predicative capability, especially when the current approaches the pile group at an angle. This study applies a Multi-Layer Perceptron Backpropagation (MLP/BP) neural network to develop a general model for predicting the local maximum equilibrium scour depth around pile groups in steady currents. The input parameters for the model include all relevant non-dimensional hydrodynamic and structural variables taking full account of the effects of the pile group arrangement and its orientation relative to the approaching current. The model’s performance was evaluated by comparing its predictions against those generated by multiple other machine learning methods, as well as against results from widely used empirical formulas. A comprehensive sensitivity analysis is carried out to determine the importance ranking of the input parameters on model accuracy.