The development of underwater high-precision navigation technology is of great significance for the application of autonomous underwater vehicles (AUVs). Traditional long baseline (LBL) positioning systems require pre-deployment and the calibration of multiple beacons, which consumes valuable time and manpower. In contrast, the range-only single-beacon (ROSB) positioning technology can help autonomous underwater vehicles (AUVs) obtain accurate position information by deploying only one beacon. This method greatly reduces the time and workload of deploying beacons, showing high application potential and cost ratio. Given the operational constraints of AUV open-ocean navigation with single-beacon weak observations and absence of valid a priori positioning data in calibration zones, a multi-sensor underwater virtual beacon localization framework was established, proposing a differential Chan–Gauss–Newton (DCGN) methodology for submerged vehicles. Based on inertial navigation, the method uses the distance measurement information from a single beacon and observations from multiple sensors, such as the Doppler velocity log (DVL) and pressure sensor, to obtain accurate position estimates by discriminating the initial position of multiple hypotheses. A simulation experiment and lake test show that the proposed method not only significantly improves the positioning accuracy and convergence speed, but also shows high reliability.