Abstract Safety assurance remains paramount for the realization of autonomous vessels. A robust assurance methodology that can provide traceability throughout the design and verification process is necessary to demonstrate safety equivalence to that of conventional ships. However, there are few references that propose a holistic safety assurance scheme for autonomous ships, using actual engineering processes of ships as examples. This study proposes a design and development method for an autonomous navigation system that integrates Model-Based Systems Engineering (MBSE), System Theoretic Process Analysis (STPA), Failure Modes and Effects Analysis (FMEA), and several verification methods including simulation-based tests to develop a comprehensive safety assurance scheme. This safety assurance scheme is being conducted as a case study for a newly constructed autonomous vessel. First, STPA can be performed on the conceptual design established by MBSE to extract additional safety requirements from the identified loss scenarios. Focusing on the process model in the loss scenario description leads to a deeper understanding of the system behavior. FMEA in addition identify potential component failure modes and their impact on system safety. The multi-level requirements that emerge from these activities are validated in test scenarios. Simulators are used to evaluate whether the autonomous navigation system’s safety can meet predefined pass criteria in some of the scenarios. These activities ensure traceability from safety goals to design decisions, allowing design changes and their impact on safety to be evaluated throughout the development lifecycle and allowing for more systematic ongoing monitoring during operations.