This study looked into the connection between the chemistry achievement of secondary school students in Anambra State, Nigeria, and their self-esteem. Gender's moderating effect on the correlation between these two factors was also identified. For the study, a correlation design was employed. Using purposive and simple random sampling techniques, 210 secondary school II Chemistry students were selected as the sample size. The instruments used were Chemistry Self-Esteem Scale (CSES) and Chemistry Achievement Test (CAT). The reliability indices of 0.88 and 0.82 were obtained for CSES and CAT respectively. For data analysis, ANOVA regression, Pearson correlation, and coefficient of determination were applied. The findings of the study revealed a moderate positive relationship between self-esteem and students’ achievement in Chemistry which was significant. Furthermore, there was a noteworthy impact of gender on the correlation between students' achievement in Chemistry and their self-esteem. Thus, it was suggested, among other things, that parents and Chemistry teachers keep an eye on and support male and female students in developing higher self-esteem. Also, there should be workshops and seminars organized by the educational stakeholders on how to improve Chemistry students’ self-esteem in order to enhance their achievement in the subject.