University student life is an important transformation stage with many potential factors that can impact negatively on the Quality of Life (QOL) and the adoption of unhealthy behaviors. Health literacy (HL), Health Behaviors (HBs), and Body Mass Index (BMI) have been found to be essential components in influencing QOL, in addition to socioeconomic determinants. To identify the influential factors of QOL, we performed a cross-sectional survey in a university, and 955 undergraduate students were enrolled as respondents. We measured two different aspects of HL, i.e., Comprehensive Health Literacy (CHL) and Functional Health Literacy (FHL). Overall, QOL scores in four domains did not differ, regarded as medium with averages ranging from 57.00–63.98, and no significant difference between male and female students. In multivariate analysis, CHL had a significant positive influence on all domains, while FHL only affected the psychological and environmental domains with negative associations. Academic performance had a significant positive association with physical and psychological domains. Students from education majors had higher QOL in the psychological and social domains. Moreover, students with normal or underweight BMI status had better psychological QOL, and physical exercise had a positive association with the social relationship and environmental domains. The findings confirmed that CHL and FHL had significant associations with QOL domains in different ways that should be addressed accordingly. Public health practitioners should carefully empower students to use both CHL and FHL as decision-making skills by incorporating them into related curricula.