Summary: A high-order compact scheme for 2D Laplace and Poisson equations under a non-uniform grid setting is developed. Based on the optimal difference method, a nine-point compact difference scheme is generated. Difference coefficients at each grid point and source term are derived. This is accomplished through the consideration of compatibility between the partial differential equation and its difference discretization. Theoretically, the proposed scheme has third- to fourth-order accuracy; its fourth-order accuracy is achieved under uniform grid settings. Two examples are provided to examine performance of the proposed scheme. Compared with the traditional five-point difference scheme, the proposed scheme can produce more accurate results with faster convergence. Another reference scheme with the same nine-point grid stencil is derived based on the five-point scheme. The two nine-point schemes have the same coefficients for each grid points; however, their coefficients for the source term are different. The overall accuracy level of the solution resulting from the proposed scheme is higher than that of the nine-point reference scheme. It is also indicated that the smoothness of grids has significant effects on accuracy and convergence of the solutions; efforts in optimizing the grid configuration and allocation can improve solution accuracy and efficiency. Consequently, with the proposed method, solution under the non-uniform grid setting with appropriate grid allocation would be more accurate than that under the uniform-grid manipulation, with the same number of grid points.