The quality and performance of steel castings is always a concern due to porosities formed during solidification of the melt. Nowadays, computational tools are playing a pivotal role in analyzing such defects, followed by their minimization through mold design optimization. Even if the castings are produced with defects in a permissible range, it is important to examine their service life and performance with those defects in a virtual domain using simulation software. This paper aims to develop a methodology with a similar idea of simulation-based optimization of mold design and predictions of life and reliability of components manufactured with minimized casting defects, especially porosities. The cast parts are standard fatigue specimens which are produced through an optimized multi-cavity mold. X-ray imaging is done to determine the soundness of cast parts. Experimental work includes load-controlled fatigue testing under fully reversed condition. The fatigue life of specimens is also simulated and compared with the experimental results. The classical strength-stress model is used to determine the reliability of cast parts through which a safe-load induced stress of steel castings is determined. Finally, probability distributions are fit to the reliability results to develop the reliability models. It is found that porosities can be minimized significantly in the mold design phase using casting simulations. Nevertheless, some porosities are bound to exist, which must be included in realistic estimation of fatigue life and reliability of cast parts.