In this paper, we developed an exact analytical 3D elasticity solution to investigate mechanical behavior of a thick multilayered anisotropic fiber-reinforced pressure vessel subjected to multiple mechanical loadings. This closed-form solution was implemented in a computer program, and analytical results were compared to finite element analysis (FEA) calculations. In order to predict through-thickness stresses accurately, three-dimensional finite element meshes were used in the FEA since shell meshes can only be used to predict in-plane strength. Three-dimensional FEA results are in excellent agreement with the analytical results. Finally, using the proposed analytical approach, we evaluated structural damage and failure conditions of the composite pressure vessel using the Tsai–Wu failure criteria and predicted a maximum burst pressure.