This report outlines the process of malaria elimination in two municipalities, São Francisco do Sul and Araquari, located in Santa Catarina, Southern Brazil, from 1980 to 1985. Before 1948, Santa Catarina reported an annual average of nearly 60,000 malaria cases. The primary vector responsible for transmission was Anopheles (Kerteszia) cruzii, which exhibited high infestation levels in endemic areas. Malaria control measures in the state began in 1941 with the involvement of the National Malaria Service. The elimination process initially targeted Plasmodium falciparum and Plasmodium malariae infections, followed by a focus on Plasmodium vivax infections in 1962. Between 1980 and 1985, comprehensive efforts were undertaken in both municipalities to control and eliminate malaria. These efforts included bromeliad removal, DDT spraying, Malathion fogging, enhanced active and passive detection measures, and serological surveys to guide the radical cure of vivax malaria with chloroquine and primaquine. As a result of these interventions, both cities witnessed a significant decline in malaria incidence, going from 6.7 cases per 1000 residents to 0 cases in 1985. This report documents the first use of serology testing and treating in malaria elimination actions, demonstrating its potential to optimize resources by targeting treatment. The success of the combined interventions underscores the importance of significant resources, sustained effort, and political commitment to achieving elimination. The feasibility of serology-guided strategies in the 1980s highlights their continued relevance today as a model for achieving malaria elimination in endemic regions.