Reinforced concrete slabs, as the main load-bearing components in the structure of construction projects, are very likely to suffer serious damage in explosive accidents, while polyurea elastomers, with their better anti-blast and anti-impact properties, have been widely used in the field of protective engineering. It is well known that the mechanical properties and deformation mechanisms of thin slabs in the range from 100 mm to 250 mm and thick concrete slabs above 250 mm are not the same, and the thickness of reinforced concrete substrates studied so far is generally concentrated in the range from 100 mm to 250 mm, and there are relatively few studies on thick slabs of polyurea-coated reinforced concrete with a slab thickness of 250 mm or more. In order to study the anti-blast performance of the polyurea/reinforced concrete thick slab composite structure, firstly, the contact explosion experiments were carried out on the polyurea/reinforced concrete thick slab composite structure with different charges, while the overall and local damage characteristics were analyzed. Secondly, numerical simulations were carried out using LS-DYNA finite element simulation software to verify the correctness of the numerical model by comparing with the experimental results. Based on LS-DYNA finite element simulations, the damage process of polyurea/reinforced concrete thick plate composite structure and the evolution of shock wave inside the polyurea/reinforced concrete thick plate were investigated, which revealed the anti-blast mechanism of the polyurea coating, and further analyzed the damage mode and damage characteristics of the polyurea/reinforced concrete thick plate composite structure. The experimental and finite element results showed that the polyurea/steel-reinforced concrete composite structure exhibited six damage modes under the contact explosion load (i.e., crate; spall; spall and bulge; threshold spall, bulging deformation of the polyurea coating; severe spall, serious bulging deformation of the polyurea coating; perforation). The investigation also demonstrated that the backside polyurea-coated reinforced concrete thick slabs effectively improved the anti-blast performance of the composite structure. The results of the study can provide a basis and reference for the design of blast resistance of polyurea/reinforced concrete thick slab composite structures.