The present paper comprises the experimental and numerical analysis of damage and fracture behavior of ductile metals under non-proportional loading with compression and shear preloading. For this purpose, biaxial experiments with the H-specimen using a pneumatic downholder for compression loading followed by failure under a tension stress state and corresponding numerical simulations are performed and analyzed. A thermodynamically consistent anisotropic continuum model is presented. It takes the effects of micromechanical damage mechanisms on the macro scale behavior as a motivation for a phenomenological description of damage behavior as a function of stress state. The experimental findings are compared with the results of tests with proportional load paths and corresponding numerical simulations. Thereto, strain fields of the critical areas of the specimens are analyzed by means of digital image correlation (DIC) technique. Compression and shear preloading can lead to significantly reduced ductility of the material with initiation of failure processes in the small damage strain range. Evolution of numerically predicted plastic and damage equivalent strains illustrates their stress state dependence. The numerical results are also confirmed by images of fracture surfaces taken by scanning electron microscopy (SEM). This experimental-numerical methodology is therefore an efficient tool to develop and validate general modeling approaches, and it is characterized by almost arbitrarily definable load paths with changes in stress states occurring in forming processes.