Reinforced concrete skew slabs are commonly used in bridges due to space constraints in motorways and in congested urban areas. Such slabs also often need to contain openings for architectural requirements or services, and this study seeks to determine the effect of these openings on the strength of the skew slabs. The finite element method was used to analyze 13 cases of slabs with skew angles of 45°. The first and second cases were used to validate the results with experimental work. Other cases studied the effect of the position and shape of openings on the strength of the skew slabs under both one-point and four-point loading conditions. The study also showed that the worst location for the opening was near the obtuse corners since this is where most of the load is transferred. With respect to the shape of openings, three different shapes with the same area were used: skew, circle, and square shapes. It was found that the effect of the opening shape depends on how many steel reinforcements are removed, as well as the appearance of negative cracking brought on as a result of the opening. Overall, the square shape introduces the smallest reduction in the skew slab strength compared with a slab with no opening. Accordingly, the study recommends that the strength of skew slabs can best be maintained if square openings are employed near the acute corners, alongside negative steel reinforcement to avoid cracking.