Fatigue cracking is one of the most critical failure types in flexible pavements under the application of repeated wheel loads. The application of vehicular load induces micro-cracks with each application eventually causing macro-cracks and failure. The chances of crack propagation multiply if a brittle cement-treated base layer lies underneath, as in the case of an inverted pavement. This study investigates the fatigue cracking in inverted pavements considering the effect of the brittleness of an underlying cemented layer. Several specimens were manufactured and tested in a wheel tracking environment while crack initiation and propagation were carefully monitored using a GoPro camera. A mechanics-based methodology has been developed to calculate the critical horizontal tensile strain at the bottom of the hot mix asphalt surface layer, which has been related to fatigue life by a fatigue prediction model. It is observed that the laboratory results are in close correlation with the predicted fatigue life. The developed approach has also been successfully applied to real pavements, constituting an important development in fatigue life prediction in inverted pavements.