In this paper, the development of a hierarchical control, path planning, and obstacle avoidance system for autonomous operation of Unmanned Sea Surface Vehicles (USSVs) in uncertain cluttered environments (e.g., littoral environments) is described. The system is designed with a modular structure incorporating a robust inner-loop controller and a hierarchical combination of wide-area, intermediate-area, and local-area planning and obstacle avoidance algorithms. The performance of the proposed system has been demonstrated through Hardware-In-The-Loop (HITL) and experimental tests. The HITL simulation platform incorporates detailed dynamics of the USSV including hydrodynamic effects as well as emulation of sensors and instrumentation onboard the USSV including Radar. The HITL platform can simultaneously simulate multiple USSVs and passive obstacles and provides the computer which runs the controls and obstacle avoidance algorithms with the exact environment which it sees when operating in the experimental USSV testbed.