In this paper, a novel numerical solution technique, the differential cubature method is employed to study the buckling problems of thick plates with arbitrary quadrilateral planforms and non-uniform boundary constraints based on the first order shear deformation theory. By using this method, the governing differential equations at each discrete point are transformed into sets of linear homogeneous algebraic equations. Boundary conditions are implemented through discrete grid points by constraining displacements, bending moments and rotations of the plate. Detailed formulation and implementation of this method are presented. The buckling parameters are calculated through solving a standard eigenvalue problem by subspace iterative method. Convergence and comparison studies are carried out to verify the reliability and accuracy of the numerical solutions. The applicability, efficiency, and simplicity of the present method are demonstrated through solving several sample plate buckling problems with various mixed boundary constraints. It is shown that the differential cubature method yields comparable numerical solutions with 2.77-times less degrees of freedom than the differential quadrature element method and 2-times less degrees of freedom than the energy method. Due to the lack of published solutions for buckling of thick rectangular plates with mixed edge conditions, the present solutions may serve as benchmark values for further studies in the future.