Solving river engineering problems typically requires river flow characterization, including the prediction of flow depth, flow velocity, and flood extent. Hydraulic models use governing equations of the flow in motion (conservation of mass and momentum principles) to predict the flow characteristics. However, solving such equations can be substantially expensive, depending upon their spatial extension. Moreover, modeling two- or three-dimensional river flows with high-resolution topographic data for large-scale regions (national or continental scale) is next to impossible. Such simulations are required for comprehensive river modeling, where a system of connected rivers is to be simulated simultaneously. Machine Learning (ML) approaches have shown promise for different water resources problems, and they have demonstrated an ability to learn from current data to predict new scenarios, which can enhance the understanding of the systems. The aim of this paper is to present an efficient flood simulation framework that can be applied to large-scale simulations. The framework outlines a novel, quick, efficient and versatile model to identify flooded areas and the flood depth, using a hybrid of hydraulic model and ML measures. To accomplish that, a two-dimensional hydraulic model (iRIC), calibrated by measured water surface elevation data, was used to train two ML models to predict river depth over the domain for an arbitrary discharge. The first ML model included a random forest (RF) classification model, which was used to identify wet or dry nodes over the domain. The second was a multilayer perceptron (MLP) model that was developed and trained by the iRIC simulation results, in order to estimate river depth in wet nodes. For the test data the overall accuracy of 98.5 percent was achieved for the RF classification. The regression coefficient for the MLP model for depth was 0.88. The framework outlined in this paper can be used to couple hydraulics and ML models to reduce the computation time, resources and expenses of large-scale, real-time simulations, specifically for two- or three-dimensional hydraulic modeling, where traditional hydraulic models are infeasible or prohibitively expensive.