This paper investigates the influence of mixture morphologies and microstructures on oxidative ageing of asphalt mixtures. For this, an oxidative ageing mechanism based on a diffusion-reaction process was developed. Previously, most asphalt oxidative ageing modeling research focused on unidirectional diffusion of continuous oxygen flow through bitumen films, which is far from the actual boundary conditions in asphalt mixtures. For this reason in the current study, a finite element (FE) analysis has been conducted in which 3D mixture morphology was considered. Mixture morphology is the combination of mineral aggregate packing, porosity, air-void distribution and their interconnectivity. One dense and one open graded field asphalt mixture core were scanned with a computerized tomography X-ray scanner. In the analyses, the developed oxidative ageing model was implemented. The FE analysis showed that the effect of the air-void distribution, their interconnectivity and the mineral aggregate packing has a significant effect on the resulting age hardening of the overall mixture. Furthermore, from the microstructural investigation done in this research, strong indications were found that, depending on the bitumen and its conditioning, water soluble thin films are formed due to ageing. This means that ageing and moisture damage are strongly interlinked and this should thus be considered in the design of the asphaltic materials and the prediction of their long term performance.