Cognitive scientists have previously shown that students’ perceptions of their learning and performance on assessments often do not match reality. This process of self-assessing performance is a component of metacognition, which also includes the practice of thinking about one’s knowledge and identifying and implementing strategies to improve understanding. We used a mixed-methods approach to investigate the relationship between students’ perceptions of their performance through grade predictions, their metacognitive reflections after receiving their grades, and their actual performance during a semester-long introductory genetics course. We found that, as a group, students do not display better predictive accuracy nor more metacognitive reflections over the semester. However, those who shift from overpredicting to matching or underpredicting also show improved performance. Higher performers are overall more likely to answer reflection questions than lower-performing peers. Although high-performing students are usually more metacognitive in their reflections, an increase in a student’s frequency of metacognitive responses over time does not necessarily predict a grade increase. We illustrate several example trends in student reflections and suggest possible next steps for helping students implement better metacognitive regulation.