Cast parts usually inherit internal defects such as micro shrinkage pores due to the manufacturing process. In order to assess the fatigue behaviour in both finite-life and long-life fatigue regions, this paper scientifically contributes towards a defect-based fatigue design model. Extensive fatigue and fracture mechanical tests were conducted whereby the crack initiating defect size population was fractographically evaluated. Complementary in situ X-ray computed tomography scans before and during fatigue testing enabled an experimental estimation of the lifetime until crack initiation, acting as a significant input for the fatigue model. A commonly applied fatigue assessment approach introduced by Tiryakioglu was modified by incorporating the long crack threshold value, which additionally enabled the assessment of the fatigue strength in the long-life fatigue regime. The presented design concept was validated utilising the fatigue test results, which revealed a sound agreement between the experiments and the model. Only a minor deviation of up to about five percent in case of long-life fatigue strength and up to about 9% in case of finite-lifetime were determined. Thus, the provided extension of Tiryakioglu’s approach supports a unified fatigue strength assessment of cast aluminium alloys in both the finite- and long-life regimes.