This study aimed at examining the extent to which metacognitive self-regulation and chemistry self-efficacy predicted critical thinking. Three hundred sixty-five university students participated in the study. Data were collected using appropriate dimensions of Motivated Strategies for Learning Questionnaire and College Chemistry Self-Efficacy Scale. Cronbach's alpha coefficients ranged from 0.77 to 0.88. Data were analyzed using structural equation modeling. Results indicated that metacognitive self-regulation was found to be positively and significantly related to chemistry self-efficacy for cognitive skills and chemistry self-efficacy for everyday applications. In addition, there was a positive and significant relationship between chemistry self-efficacy for everyday applications and critical thinking, whereas there was no significant relationship between chemistry self-efficacy for cognitive skills and critical thinking. Overall, the tested model explained 68.5% of critical thinking. Findings provide suggestions in order to enhance critical thinking in chemistry classes.