The proposed paper presents the design and development of the combined guidance and control strategies for the autonomous navigation of an unmanned vessel characterized by azimuth-based thrust architecture. Autonomous Marine Vehicles (AMVs) are consolidates technological tools commonly employed for different tasks such as exploration, sampling and intervention. With the final aim of autonomous shipping, the capabilities of AMVs have to be migrated and adapted towards the reliable and safe control of commercial-like unmanned vessel, that are taking place thanks to a number of technological research projects. The employment of new concept hulls and thrust configurations, as for instance Small Waterplane Area Twin Hull (SWATH) combined with Azimuthal propulsion (common propeller-based thruster with the capability of 360◦ rotation around the vertical axis), requires robust guidance techniques to provide precise and reliable motion control during navigation. The paper proposes a dual-loop guidance and control scheme able to provide advanced navigation capabilities. In particular, the inner control loop, devoted to the actuation of the azimuthal thrusters, allows the tracking of reference course angle (namely the autopilot). Such a control loop is characterized by a modified PID regulation scheme, where a novel adaptive derivative component is inserted in order to improve the convergence curve towards the required course reference. The outer guidance loop, based on Lyapunov/virtual-target approach, allows the vessel to track generic desired paths, thus enhancing the autonomous navigation capabilities also in constrained environments. The paper will provide a deep design and analysis approach for the developed techniques, as well as simulation results of the combined guidance and control scheme, proving the reliability of the proposed approach in different operative conditions. Experimental results will be provided, depending on the availability of the actual autonomous vessel (currently under final development/test phases and related to the specific project activities).