Hydrodynamic pressure sensors offer an auxiliary approach for ocean exploration by unmanned underwater vehicles (UUVs). However, existing hydrodynamic pressure sensors often lack the ability to monitor subtle hydrodynamic stimuli in deep-sea environments. In this study, we present the development of a deep-sea hydrodynamic pressure sensor (DSHPS) capable of operating over a wide range of water depths while maintaining exceptional hydrodynamic sensing performance. The DSHPS device was systematically optimized by considering factors such as piezoelectric polyvinylidene fluoride–trifluoroethylene/barium titanate [P(VDF-TrFE)/BTO] nanofibers, electrode configurations, sensing element dimensions, integrated circuits, and packaging strategies. The optimized DSHPS exhibited a remarkable pressure gradient response, achieving a minimum pressure difference detection capability of approximately 0.11 Pa. Additionally, the DSHPS demonstrated outstanding performance in the spatial positioning of dipole sources, which was elucidated through theoretical charge modeling and fluid–structure interaction (FSI) simulations. Furthermore, the integration of a high Young’s modulus packaging strategy inspired by fish skull morphology ensured reliable sensing capabilities of the DSHPS even at depths of 1000 m in the deep sea. The DSHPS also exhibited consistent and reproducible positioning performance for subtle hydrodynamic stimulus sources across this wide range of water depths. We envision that the development of the DSHPS not only enhances our understanding of the evolutionary aspects of deep-sea canal lateral lines but also paves the way for the advancement of artificial hydrodynamic pressure sensors.