This study investigates the dynamic damage effects, focusing specifically on the spallation failure mechanism, in clamped steel plates subjected to impact by explosively driven flyers. A specialized device for generating explosively driven flyers was designed. Experimental observations revealed that clamped A3 steel plates exhibited a characteristic damage morphology consisting of plastic indentation on the impacted surface and spallation peeling on the free surface. The velocity of the spalled fragments was precisely measured. A fluid-structure interaction numerical model was established using AUTODYN software. The Arbitrary Lagrange-Euler (ALE) algorithm was employed to simulate the entire process encompassing detonation, flyer acceleration, impact, and the dynamic response of the steel plate. Material dynamic failure behavior was characterized by combining the Johnson-Cook constitutive model with the Grady spallation criterion. The reliability and accuracy of the numerical simulations were validated through comparison with experimental results. Leveraging this validated model, the influence of steel plate material type, loading configurations, and plate thickness on the dynamic response and spallation was systematically analyzed. Key findings reveal that high-strength steel effectively suppresses spall propagation by significantly enhancing the dynamic yield strength, resulting in a damage mode manifested as internal cavitation rather than complete spallation. The combined blast-fragment loading exhibits a significant enhancement effect on spallation, attributed to material softening within the blast-induced pre-damage zone and the resultant tensile stress concentration effect. Increasing plate thickness enhances plastic work dissipation while reducing spall fragment velocity. For A3 steel, a thickness range of 30–35 mm is identified as striking an optimal balance between blast resistance and structural efficiency.