According to various experimental results, stiffened panels under compressive loading are prone to debonding between the skin and the flange of the stringer. In this paper, a novel two-way global-local coupling approach is presented that is able to model progressive separation of the skin and stringer in stiffened CFRP panels under compression. The main goal of this methodology is to examine skin-stringer debonding at two levels of accuracy, taking advantage of the fast calculations at the global level and assessing in detail the damage propagation at the local level. First, critical areas are defined in a global model with a standard mesh, and local models with a considerably finer mesh are created by means of a submodeling technique. Secondly, a local model analysis is conducted, in which cohesive elements are applied to simulate debonding. Particularly important is the appropriate information exchange in both directions between the different steps of the coupling analysis. Averaged degraded properties are defined at the local model level and transferred back to the global level. The applied compressive load is increased and induces a progression in skin-stringer separation. The global-local coupling loops are repeated until panel failure occurs. The approach is applied to a case of a representative one-stringer stiffened panel and to a stiffened panel for which test results are available. A good correspondence with reference results and test results demonstrates the effectiveness of the global-local approach presented.