This study aimed to investigate the effects of cross-cultural competence and social support on international students’ psychological adjustment, specifically autonomy and environmental mastery in the host country, the United States. The participants in this study included 94 international students studying in the southeastern region of the United States. A series of standard multiple regression analysis were conducted to predict international students’ autonomy and environmental mastery as measured by Ryff’s Scales of Psychological Well-Being (Ryff & Keyes, 1995). The study revealed a positive relationship between international students’ autonomy and cross-cultural competence as measured by the Intercultural Competence Scale (ICC). A positive relationship was also revealed between environmental mastery and social support as measured by the Multidimensional Scale of Perceived Social Support (MSPSS). The results, however, found negative relationship between length of residency in the host country and autonomy and environmental mastery. Relationships between psychological adjustment (i.e., autonomy and environmental mastery) and gender differences and different cultural background (individualistic and collectivistic cultures) were not significant. International students, their parents, and those who work with international students may use research findings to facilitate the psychological adjustment of international students in the host country.