A probabilistic framework is developed utilizing a two-scale modeling approach to efficiently consider the material variability that is typical for composite materials. The modeling integrates a macro-scale model with effective elastic properties extracted from micro-mechanical simulations. Using a weakest link modeling approach for fatigue assessment the combined effects of defects on fatigue strength in a Carbon Fiber Reinforced Polymer (CFRP) material can be investigated. A full fatigue test program is presented and is used to calibrate the probabilistic fatigue model. By including material variability in the numerical model, the calibrated probabilistic model improves the fatigue life prediction.