<p>Shortly after its first outbreak in Wuhan, the SARS CoV-2 spread worldwide. This study determined SARS CoV-2 seroprevalence and compared anti-RBD IgG titre distributions among seropositive samples across four repeated cross-sectional surveys conducted during successive epidemic waves from August 2020 to January 2022. Age-specific seroprevalence and titre patterns were also examined across children, adolescents, and adults. We conducted a seroepidemiological cross-sectional study over four epidemic waves periods. A stratified 1,096 samples, reflecting the age and sex distribution of the Accra population, was selected from 15,000 residual clinical samples. Adjusted seroprevalence increased from 58.3% (95% CI: 53.9–62.6%) in wave 1 to &gt; 90% by wave 2 and remained ≥ 96% in waves 3 and 4. Adults aged ≥ 20 years reached near-universal seropositivity earlier than children, who accumulated exposure more gradually. Despite this early plateau, geometric mean anti-RBD IgG concentrations increased from 162 BAU/mL in wave 1 to 625 BAU/mL in wave 3, stabilising at 584 BAU/mL in wave 4. Analyses of antibody titre distributions demonstrated that progressively larger proportions of adults showed concentrations substantially exceeding wave 1 baseline levels in later waves, indicating age-related differences in cumulative antigenic exposure. Across successive epidemic waves, Accra experienced intense and repeated SARS CoV-2 transmission, resulting in near-universal exposure of the adult population by May 2021. Children and adolescents showed a slower and more gradual increase in both seroprevalence and antibody concentrations. Anti-RBD IgG titres increased across successive waves and stabilised after August–November 2021, consistent with sustained cumulative antigenic exposure at the population level.</p>