Persistence is an important indicator of academic success in higher education. Academic stress, which influences individuals' learning motivation and behaviors, is inevitable in college life; however, individuals handle it differently based on their expectancy and value beliefs. In this study, academic stress, academic self-efficacy, and task value were chosen as predictors of persistence in learning, and the joint relationship between them was examined. The sample comprised 483 Korean college students. A multiple regression analysis was performed. The results revealed significant main and interaction effects, including a three-way interaction effect of academic stress, academic self-efficacy, and task value on persistence in learning. Particularly, students with strong motivation were less affected by a stressful and demanding environment. Furthermore, academic stress did not appear to be an exclusively negative factor and could be a catalyst to boost persistence in some conditions. Implications of the findings for promoting persistence in learning are discussed.