There is emerging recognition that mechanistic reasoning about scientific phenomena as well as developing an interdisciplinary understanding of science are valuable for student success. Our team of chemistry, biology, and teacher education researchers strives to support students in their interdisciplinary learning and engage them in causal mechanistic reasoning (CMR), a thinking strategy that involves identifying underlying entities and their properties and linking these ideas to explain or predict a target phenomenon. We aim to help students build connections between their undergraduate chemistry and biology courses through engagement with carefully developed activities, which can be administered in a range of courses. In this study, we explored how students in 7 different chemistry, biology, or biochemistry courses engaged in CMR about preferential protein-ligand binding, a biological phenomenon that requires an understanding of core chemistry ideas like atomic properties and electrostatics. Explanations varied from noncausal mechanistic to fully causal mechanistic across all courses; however, students co-enrolled in molecular biology and second semester general chemistry did not differ in their engagement in CMR when situated in each course. Student responses provided evidence of activation of different conceptual resources, including charge, polarity, and space, to explain this phenomenon. Lastly, correct predictions about the preferred binding site were highly correlated with fully engaged CMR, showing compelling evidence for the power of this thinking strategy. This task effectively elicits CMR in both chemistry and biology courses, thus making it a potential tool for helping students build connections across disciplinary silos they experience in undergraduate science curricula.