2015 Taylor & Francis. In this paper, a new mechanics-based top-down fatigue cracking analysis framework is presented for asphalt pavements. A new mixture morphology-based set of material sub-models is presented for characterising key mixture properties and their change over time. Predicting the load induced top-down fatigue crack initiation (CI) time by utilising comprehensive mixture properties creates the possibility of optimising the mixture morphology while taking into account its subsequent effect on long-term pavement performance. The new framework was calibrated and subsequently validated against a number of field pavement sections with varying traffic levels that are representative for current practices and which have a wide range in material properties. The framework accounts the change in key mixture properties due to ageing and mixture-healing effect on damage accumulation while determining the overall effect of design inputs on cracking performance. Model calibration and validation were achieved based on the healing potential of the asphalt mixture. It was found out that the CI predictions for all the sections are in general agreement with the observed performance in the field, thus giving credibility for the framework.