Student success in chemistry is inherently tied to motivational and other affective processes. We investigated three distinct constructs tied to motivation: self-efficacy, interest, and effort beliefs. These variables were measured twice over the course of a semester in three sections of a first-semester general chemistry course (n = 170). We explored the connections that exist among these three constructs as well as their connections to course performance. Multiple regression and path analysis revealed that self-efficacy measured during week 12 was the strongest predictor of final course grade followed by situational interest. We also report that personal interest is a significant predictor of future self-efficacy. Our results add to the growing literature on psychological constructs within chemistry education by identifying variables related to motivation that have a significant connection to course performance among chemistry students. We briefly address how these variables could be targeted in the classroom.