This paper investigates the fatigue strength of two cast aluminium alloys, EN AC-45500 and 46200, dealing with the influence of microporosity and the statistical size effect. Small-scale round specimens are extracted from cylinder heads and crank cases as typical cast components in automotive industry. Uniaxial fatigue tests under alternating tension/compression loading are performed. Local microstructural properties, such as second dendrite arm spacing and microporosity, are characterized by means of metallography, fracture surface analysis utilizing scanning electron microscopy, and X-ray computed tomography. The measurements reveal significant differences in microporosity and microstructure depending on the extraction position and specimen type. These findings are reflected by the experimental test results showing that the microporosity majorly affects the fatigue behaviour with a maximum difference in fatigue resistance at ten million load-cycles of up to 39% in case of the EN AC-45500 specimens. Additional experiments involving two different EN AC-46200 specimen types exhibiting unequal highly-stressed volumes demonstrate a reduction of the high-cycle fatigue strength by 8% caused by the statistical size effect. Fatigue strength assessment incorporates the application of the model by Tiryakioğlu based on the extreme value distribution of the micropore sizes by Gumbel, as well as the √area approach by Murakami. The evaluated results agree well to the fatigue tests enabling a local fatigue strength assessment under consideration of manufacturing process dependent material characteristics.