Objectives: Depression and anxiety contribute to the burden of disease among college students. The current study determined if depressive and anxiety symptoms were more prevalent in first generation students and if social and emotional support moderated this relationship. Methods: Depressive and anxiety symptoms were measured in 432 U.S. college students via an online survey. Single items determined student generation status and available social support. The CES-D10 and GAD-7 measured depression and anxiety, respectively. Structural equation modeling was used to identify significant effects. Results: First generation status was associated with increased cognitive-emotional (p = 0.036) and somatic (p = 0.013) anxiety symptoms, but not depression. High social and emotional support appeared to suppress somatic anxiety symptoms experienced by first generation students (p = 0.004). Conclusions: Greater anxiety symptoms in first generation students may be due to increased general and acculturative stress, although more research is needed. Large national surveys of college students should consider adding a question about first generation status.