With the development and application of composite materials in deepwater submersibles, the influence of high external pressure from deepwater environments on the vibration characteristics of composite pressure-resistant cylindrical shells cannot be ignored. In this paper, the free vibration characteristics of prestressed composite multilayer shells are methodically examined by establishing partial differential equations based on the three-dimensional elasticity theory. To solve these equations, the state-space technique and double Fourier series expansion are employed to transform them into state-space ordinary differential equations. These equations are utilized to analyze vibration problems of simply supported composite multilayer cylindrical shells with arbitrary layered angles. The initial stress equilibrium equation is solved to determine the prestress induced by the hydrostatic pressure. This overcomes the limitation of membrane stress and considers non-uniform distributions of radial and interlaminar prestresses. The proposed theoretical model and solution strategies are validated by comparing with theoretical and experimental results from the existing literature and the finite element method. Additionally, the present investigation reveals that the natural frequencies of thick shells can be calculated more accurately using the prestress derived by the proposed approach, especially subjected to noticeable hydrostatic pressure. Finally, the performed investigations indicate that the circumferential prestressing has a more pronounced effect on the shell's natural frequencies than axial prestressing.