Background: The endorsement of unproven COVID-19 treatment marked the political bias in Brazil's pandemic response. This study aimed to analyze the trends in the consumption of azithromycin (AZI), chloroquine/ hydroxychloroquine (CQ/HCQ), and ivermectin (IVM) considering COVID-19 cases and key political events. Methods: A retrospective cohort study was conducted to analyze the weekly outpatient dispensing records of AZI, CQ/HCQ, and IVM from the National Database of Actions and Services of Pharmaceutical Services in SUS (BNAFAR) and the COVID-19 incidence rates from January 2019 to December 2021. A joinpoint regression analysis was employed to assess shifts in COVID-19 incidence rates and AZI, CQ/HCQ, and IVM consumption in outpatients, expressed as Defined Daily Dose per 1,000 inhabitants per day (DID), in Brazil and its five geographical regions taking into consideration the timing of three political events. Results: There was a significant increase in AZI, CQ/HCQ, and IVM consumption during the COVID-19 pandemic in Brazil of 62.8%, 504.6%, and 525.7%, respectively. Adults and women had higher DID; however, a higher proportional rise was observed among men, especially for CQ/HCQ. A notable increase in the consumption of CQ/HCQ during the first COVID-19 wave, IVM in the second, and AZI in both waves was more pronounced in the South, Midwest, and North of Brazil. This pattern coincided closely with the timeline of COVID-19 incidence rates and showed an upward trend in all three medicines after key political events that endorsed their use, particularly in these three regions. No corresponding downward trend in COVID-19 cases was observed despite the increased use of these medicines. A significant reduction in consumption nationwide was observed after an increase in vaccination coverage, resulting in a DID near pre-pandemic levels. Conclusion: The study provides substantial evidence on the relationship between COVID-19 incidence, political events, and the consumption of AZI, CQ/HCQ, and IVM during the pandemic in Brazil. The findings suggest that consumption trends were aligned with regional political affiliations and the COVID-19 incidence rates. These highlight the importance of political determinants of inappropriate medicine utilization that wastes scarce resources and increases the risk of adverse health outcomes and antimicrobial resistance.