The software package HEC-RAS (Hydrologic Engineering Center’s River Analysis System) is widely used by the water engineering community to analyze hydraulic systems and perform development planning. Furthermore, it integrates a control module that allows implementing basic controllers. For more complex approaches, developers from the automatic control and artificial intelligence (AI) communities usually design, implement, and test new algorithms using dedicated software such as MATLAB. However, models of hydraulic systems employed in MATLAB are often very simple. The main objective of the paper is to design a simulation architecture by coupling HEC-RAS with MATLAB, thus improving the accuracy of the dynamics of the hydraulic systems considered in the control simulations. The main feature of the MATLAB HEC-RAS interface design is that it allows one to execute customized code at regular time intervals during the simulation. In this way, closed-loop control and optimization algorithms can be implemented and tested. Moreover, the generic interface allows for any configuration of hydrographical systems. The proposed interface is presented in this paper, and the performance of the approach is demonstrated considering two case studies of different nature.