The identification of students at risk for academic failure in undergraduate chemistry courses has been heavily addressed in the literature. Arguably one of the strongest and most well-supported predictors of undergraduate success in chemistry is the mathematics portion of the SAT (SAT-M), a college-entrance, standardized test administered by the College Board. While students scoring in the bottom quartile of the SAT-M (herein referred to as at-risk) perform significantly worse on first-semester chemistry assessments, little is known of the topics on which these students differentially struggle. The purpose of this study is to provide insight as to which first-semester chemistry topics present an incommensurate challenge to at-risk students. Students were identified as either at-risk or not at-risk via SAT-M scores. Students' assessment responses were collected across four semesters of first-semester chemistry courses at a large, public university (N = 5636). At-risk students struggled consistently across all topics but disproportionately with mole concept and stoichiometry. Analyzing the trend in topics suggests that the struggles of at-risk students are not entirely attributable to topics that rely heavily on algorithms or algebraic math. Moreso, at-risk students found to have performed well on mole concept and stoichiometry went on to perform similarly as their not at-risk peers. The results support an instructional emphasis on these topics with reviewed literature offering promising, practical options to better serve at-risk students and broaden representation in the sciences.