Background: To avoid antibiotic resistance, acute respiratory infections (ARIs) require the use of appropriate antibiotics. As a result, having the appropriate knowledge and perceptions is critical for achieving successful clinical outcomes. Objective: The purpose of this study was to determine the relationships and differences in knowledge and perceptions about antibiotics and ARI in urban and suburban communities in the Karawang Regency of West Java Province, Indonesia. Methods: We used a validated questionnaire approach to conduct a cross-sectional study in primary health care facilities. We surveyed 440 respondents from urban areas and 464 respondents from suburban areas. Results: Respondents in both urban and suburban areas agreed that self-diagnosis should not be used to prescribe antibiotics. False knowledge and perceptions about antibiotic use were more prevalent in suburban respondents than urban respondents. Additionally, a significant correlation between education levels and knowledge and perception was observed in both areas. Furthermore, significant correlations between age and occupation, as well as knowledge and perceptions, were identified in urban areas. Conclusion: Our study suggests that additional efforts are needed to increase awareness and ensure appropriate antibiotic use in the community.