This study investigated the self-efficacy of first-year Chemistry students at a South African university. The research involved a quantitative survey of 333 students using the College Chemistry Self-Efficacy Scale (CCSS) developed by Uzuntiryaki and Capa Aydin (2009). Descriptive statistics on data for the CCSS scales suggested that students have positive beliefs in their capability to accomplish chemistry tasks. The students scored more strongly on the self-efficacy constructs of cognitive and psychomotor skills than on everyday application. There was a significant difference between students of different professional orientations for cognitive skills and everyday applications, with students enrolled for Chemical Engineering having the highest mean scores for these constructs. A multiple regression analysis was run in order to explore the relationship between chemistry self-efficacy and performance in a chemistry examination. The analysis indicated that cognitive skills significantly predicted chemistry performance, while psychomotor skills and everyday applications had no significant impact. The implications for research and instruction are discussed in terms of the relationship between chemistry self-efficacy and performance.