Chemistry self-efficacy has been defined as a student's beliefs about his or her own capability to perform a given chemistry task. These chemistry self-efficacy beliefs can be influenced by students' experiences in a course, and eventually, these beliefs could affect students' decisions to continue into STEM related-careers. In this study, we examined students' chemistry self-efficacy throughout a semester in a college preparatory chemistry course for science majors. Students' chemistry self-efficacy was measured five times during a semester using items from the Chemistry Attitudes and Experiences Questionnaire (CAEQ). A multilevel modeling analysis was performed with a growth curve model to examine changes in self-efficacy across the term, including the potential for differences by sex and race/ethnicity. Differences in expected CSE scores were noticeable at the beginning of the semester, but this gap was smaller by the end of the semester. Higher initial CSE scores and a negative trend as the term continued were observed for Black and Hispanic males when compared with White males. In contrast, the CSE trend for Hispanic females was found to be positive. The findings in this study showed the importance of measuring CSE beliefs at multiple time points and for students from demographic groups underrepresented in STEM fields, being alert to the potential for different CSE trajectories.