While health literacy research in mainland China has gained increasing attention, most studies focus on adults. This study aimed to examine the mediating role of health literacy in the relationship between a range of upstream factors and health behaviors among Chinese secondary students. A cross-sectional study was conducted with 650 students in Years 7 to 9 from four secondary schools in Beijing. Based on an adapted health literacy framework from Manganello, a self-administered questionnaire was designed to collect information on upstream factors, health literacy, and health behaviors. Path analysis results showed that the proposed framework was mostly supported by empirical data after modification indices were examined and 3 direct paths were added. Students’ self-efficacy, social support, and school environment were associated with health literacy, which in turn predicted health behaviors. A holistic approach is needed to improve both adolescent health literacy and health behaviors for Chinese school-aged adolescents.