Feeling a sense of belonging in a learning environment can have positive effects on student success. The impact of this psychosocial variable on undergraduates’ achievement and retention has been demonstrated in STEM disciplines, especially for women within physical sciences where large disparities in gender representation persist. The current study explores the relationship between belonging and student success in undergraduate chemistry, where greater gender parity has recently emerged. In particular, this research investigates the belonging of first-year students enrolled in a two-semester General Chemistry course sequence. The study begins by examining whether students’ early sense of belonging in the course, indexed by two survey measures (perceived belonging, belonging uncertainty) varies depending on their demographics and academic preparation. The belonging measures are then used as predictors of performance in General Chemistry 1 and 2 and attrition from one semester to the next. Paralleling research in other STEM disciplines, the results show that female students, especially those from underrepresented minority groups, reported lower belonging and higher uncertainty than male students within the first weeks of the course. After accounting for demographics, preparation, and participation in a course supplemental program, the belonging measures predicted performance and attrition for all students. These findings suggest that course-level belonging in General Chemistry can have practical consequences for student success, and early disparities in belonging may have downstream effects on the retention of women and other groups underrepresented in STEM. Strategies for creating an inclusive and engaging environment that supports the success of all students are discussed.