Abstract: This study systematically investigates the fluid-structure interaction (FSI) mechanisms and resonance vulnerabilities of a low-head radial gate subjected to flow-induced vibrations (FIV) resulting from bottom seal failure under long-term water-retaining conditions. Utilizing a high-fidelity three-dimensional FSI numerical model, comprehensive analyses—encompassing dry and wet modal extraction, fluctuating pressure spectral evaluation, resonance safety assessment, and transient dynamic response characterization—were conducted across 24 computational scenarios. These scenarios account for varying degrees of localized seal degradation (1 m, 2 m, and 3 m partial loss, together with complete failure) combined with six distinct operational water level differentials. The principal findings and conclusions are summarized as follows: (1) Comparative modal analyses highlight the profound influence of the fluid domain on the structural dynamic characteristics of the radial gate. Under dry conditions, the first 20 natural frequencies range from 7.600 Hz to 33.506 Hz, exhibiting complex spatial deformations involving panel bending, structural arm torsion, and supporting frame deflection. However, incorporation of the hydrodynamic added-mass effect under wet conditions induces a substantial reduction in these natural frequencies, resulting in an overall decrease of 60% to 70%. The fundamental frequency decreases markedly from 7.600 Hz to an ultra-low band of 2.095–2.358 Hz. Crucially, the structural mode shapes undergo a fundamental transition into low-frequency modes exclusively dominated by the pontoon, indicating it as the primary structural weak link under continuous hydrodynamic loading. (2) Spectral analysis of the fluctuating pressure field demonstrates that the unsteady leakage flow induced by localized seal damage serves as the primary mechanical excitation source. Irrespective of the water level combinations or the spatial extent of seal damage, the dominant hydrodynamic excitation frequencies consistently cluster near 4 Hz and 9 Hz. Transient dynamic response analyses reveal that in 21 of the 24 scenarios, the pressure time-history exhibits a rapidly decaying trend—stabilizing within 1.5 s—indicating efficient dissipation of excitation energy by inherent system damping. Conversely, under the critical conditions of a 1 m partial seal loss coupled with water level combinations of 3.0 m/2.5 m (outer/inner river) and 4.4 m/3.1 m, the structure exhibits sustained, non-decaying harmonic oscillation. In these scenarios, the dominant fluid excitation frequency (4.00 Hz) aligns precisely with the pontoon-dominated natural frequency band (3.27–4.35 Hz). This frequency overlap, coupled with sufficient hydrodynamic load intensity, induces severe and continuous resonance, yielding a steady-state vibration displacement of 16.8–17.6 mm at the pontoon apex, substantially exceeding permissible dynamic safety thresholds. (3) A counterintuitive, non-monotonic correlation is identified between the spatial scale of seal damage and the resultant structural resonance risk. Quantitative results demonstrate that localized, small-scale seal defects (e.g., 1 m loss) generate highly concentrated leakage jets and intensified local fluctuating pressure gradients. Paradoxically, this mechanism yields a markedly higher resonance probability and greater dynamic displacement than larger-scale defects, providing a critical paradigm shift for maintenance strategies by prioritizing early interventions for minor seal defects. (4) Based on the elucidated FSI mechanisms, a comprehensive full-chain vibration mitigation strategy is synthesized, integrating excitation source control, structural dynamic tuning, and intelligent state management. At the source control tier, a primary-auxiliary dual-seal paradigm is advocated, featuring an optimal pre-compression ratio of 20%–30% and rigorous installation tolerances (local flatness deviation ≤ 0.2 mm/100 mm; cumulative straightness deviation ≤ L/1500, where L represents seal length). Additionally, geometric optimization of the pontoon's bottom plate with an upward deflection angle of 8° ± 2° is proposed to deflect leakage jets toward the free surface, thereby suppressing periodic pressure pulsations. At the structural tuning tier, integrating internal stiffening ribs or tuned mass dampers (TMD) within the pontoon cavity is suggested to proactively shift structural frequencies away from the 4 Hz and 9 Hz excitation bands, optimizing TMD parameters for maximum supplementary damping at the 4 Hz target frequency. At the operational management tier, the deployment of a multi-source structural health monitoring (SHM) system—integrating vibration, acoustic emission, strain, and hydrodynamic pressure data—is recommended, coupled with an intelligent early-warning framework driven by digital twin technology and machine learning algorithms (e.g., Random Forest, LSTM) for real-time state perception and predictive maintenance. In conclusion, this research clearly identifies two high-risk resonance scenarios requiring strict avoidance during gate operation. The proposed full-chain mitigation strategy establishes a robust theoretical foundation and an actionable technical roadmap for the anti-vibration design, structural retrofitting, and intelligent lifecycle management of similar low-head hydraulic radial gates.