Women, underrepresented minorities, and low-income students remain underrepresented in STEM disciplines. Among the required introductory courses, the calculus sequence is an obstacle linked to students’ decisions to leave their chosen discipline. Here, we analyzed data on students’ grades across the calculus sequence at a Minority-Serving Institution and examined the following: (a) group-level disparities in performance and the evolution of these disparities over the course sequence, (b) whether and how disparities in performance relate to differences in persistence rates between groups, and (c) whether course grades are linked to underrepresented students’ decisions to continue with subsequent coursework. Findings suggest that the barriers in pursuing STEM majors differ among underrepresented groups and have implications for efforts aimed at diversifying the STEM pipeline.