Influenza A and B viruses pose significant global health threats, with substantial impacts on morbidity and mortality. Understanding their molecular epidemiology in Brazil, a key hub for the circulation and dissemination of these viruses in South America, remains limited. This study, part of the Center for Viral Surveillance and Serological Assessment (CeVIVAS) project, addresses this by analyzing data and samples from all Brazilian macroregions, along with publicly available sequences from 2021-2023. Phylogenetic analysis of the Hemagglutinin (HA) segment of Influenza A/H1N1pdm09, A/H3N2, and Influenza B/Victoria-lineage revealed the predominance of A/H3N2 2a.3 strain in 2021 and early 2022. This was succeeded by A/H3N2 2b until October 2022, after which A/H1N1pdm09 5a.2a and 5a.2a.1 lineages became prevalent, maintaining this status throughout 2023. B/Victoria circulated at low levels between December 2021 and September 2022, becoming co-prevalent with A/H1N1pdm09 5a.2a and 5a.2a.1 lineages. Comparing the vaccine strain A/Darwin/9/2021 with circulating A/H3N2 viruses from 2021-2023 revealed shared mutations to aspartic acid at residues 186 and 225, altering the RBD domain´s charge. For A/H1N1pdm09, the 2022 consensus of 5a.2a.1 and the vaccine strain A/Victoria/2570/2019 had 14 amino acid substitutions. Key residues such as H180, D187, K219, R223, E224, and T133 are involved in hydrogen interactions with sialic acids, while N130, K142, and D222 may influence distance interactions based on docking analyses. Distinct Influenza A lineage frequency patterns across Brazil´s macroregions underscore regional variations in virus circulation. This study characterizes the dynamics of Influenza A and B viruses in Brazil, offering valuable insights into their circulation patterns. These findings have significant public health implications, informing strategies to mitigate transmission risks, optimize vaccination efforts, and enhance outbreak control measures.