To understand the reasons for the public’s irrational use of antibiotics based on the health belief model (HBM). A questionnaire survey was conducted based on cluster random sampling in Chongqing, China. The public’s antibiotic use behaviors, knowledge, perceived threat of diseases [both short-term upper respiratory tract infections (URTIs) and long-term antibiotic resistance (AR)], perceived value of antibiotic use (benefits and harm), self-efficacy, antibiotic availability and social influences were measured. Structural equation modeling (SEM) was applied to test the fitness of the survey data with the theoretical framework based on the HBM. A total of 815 respondents were enrolled. The irrational use of antibiotics was prevalent among the public (mean: 2.95, SD = 2.12). The public had limited knowledge about antibiotic use (average 29.17% correct answers to 8 questions), a high perceived threat of AR (mean = 2.46, SD = 0.64) and a moderate perceived threat of URTIs (mean = 2.13, SD = 1.04). They also perceived high benefits (mean = 2.57, SD = 0.68) and moderate harm (mean = 2.16, SD = 0.83) from antibiotic use. In addition, respondents had easy access to antibiotics (mean = 2.38, SD = 0.80), perceived a high prevalence of use of antibiotics by relatives (mean = 2.40, SD = 0.65) and had a moderate level of self-efficacy in using antibiotics (mean = 1.97, SD = 0.75). The SEM results showed that higher levels of the perceived threat of URTIs, perceived benefits of antibiotic use, self-efficacy, antibiotic availability and social influence were associated with more irrational antibiotic use behavior (p < 0.005). Moreover, higher knowledge indirectly led to irrational use of antibiotics by promoting self-efficacy (p < 0.001) and the perceived threat of URTIs (p < 0.005). To curb the irrational use of antibiotics, improving knowledge alone is insufficient. A systematic approach addressing multiple dimensions of health beliefs is critical. This includes: (1) targeted public education campaigns emphasizing the limited efficacy of antibiotics for viral infections and reframing perceptions of antibiotic “benefits”; (2) regulatory measures to restrict non-prescription antibiotic sales in pharmacies; (3) clinical guidelines and training to reduce unnecessary antibiotic prescriptions by healthcare providers; and (4) community-level interventions leveraging social norms to discourage inappropriate antibiotic use. Policymakers should prioritize interventions that address both individual perceptions (e.g., fear of untreated infections) and systemic drivers (e.g., antibiotic accessibility).