The numerical investigation is performed on the vibration of the higher order shear deformable carbon nanotube reinforced composite (CNTRC) spherical panels subjected to the initial external pressure. The functionally graded nanocomposite is reinforced with the non-uniform distribution of CNTs. The problem is formulated following the higher order shear deformation shell theory (HSDT) within the variational differential quadrature numerical approach. For this purpose, the direct discretization of Hamilton’s principle is carried out with the aid of differential quadrature operators. Derivation of the variational formulation of nanocomposite spherical panels based on the HSDT and studying the effects of external pressure on the vibration behavior are the main novel aspects of this research. Several numerical examples are provided to survey the impacts of geometrical and material factors on the vibration of pressurized functionally graded CNTRC spherical panels. It is shown that the internal pressure has the most influence on the vibrational behavior of the thicker panel.