Background: Every year, young adults with chronic conditions matriculate into college, which is a unique transitional period in that students may be managing a chronic condition on their own for the first time. Therefore, it is important to examine which factors may contribute to positive health behaviors and risky behaviors in college students with chronic conditions. Purpose: The current study examined associations between health literacy, self-efficacy, and health behaviors in a sample of college students with chronic conditions. Methods: Data were collected from 147 undergraduate students at a Mid-Atlantic U.S. university. Students completed an online consent and questionnaires assessing chronic conditions, health literacy, self-efficacy, and health behaviors (general behavior, wellness maintenance, substance use). Results: Asthma was the most prevalent self-reported chronic condition (26.1%). Higher levels of health literacy and self-efficacy were significantly associated with general health behaviors and wellness maintenance and fewer substance use behaviors. Discussion: These findings highlight health literacy and self-efficacy as potential foci for maintaining healthy behaviors in college students with chronic conditions. Translation to Health Education Practice: College health centers are important facilitators of promoting college student health. Incorporating health literacy and self-efficacy into Health Education interventions could be effective in improving student health.