In this paper, we develop domain decomposition spectral method for mixed inhomogeneous boundary value problems of high order differential equations defined on unbounded domains. We introduce an orthogonal family of new generalized Laguerre functions, with the weight function x ? , ? being any real number. The corresponding quasi-orthogonal approximation and Gauss-Radau type interpolation are investigated, which play important roles in the related spectral and collocation methods. As examples of applications, we propose the domain decomposition spectral methods for two fourth order problems, and the spectral method with essential imposition of boundary conditions. The spectral accuracy is proved. Numerical results demonstrate the effectiveness of suggested algorithms.