In the contemporary work environment, which is characterized by change and uncertainty, employees must proactively manage their careers to develop and maintain their competitiveness. Drawing on self-determination theory, this study developed an interactive model that uses job autonomy, supervisor support, and calling to predict career self-management. With a sample of 245 full-time employees in China, the time-lagged survey showed that job autonomy has a direct effect on career self-management, which is moderated by supervisor support and employees’ calling. Furthermore, the three-way interaction indicated that the moderating effect of supervisor support on the relationship between job autonomy and career self-management is stronger when calling is low. Finally, the implications, limitations, and future research directions are discussed.