In May 2023 the World Health Organization (WHO) declared the end of COVID-19 as a public health emergency. Seroprevalence studies performed in African countries, such as Cameroon, depicted a much higher COVID-19 burden than reported by the WHO. To better understand humoral responses kinetics following infection, we enrolled 333 participants from Yaoundé, Cameroon between March 2020 and January 2022. We measured the levels of antibodies targeting the SARS-CoV-2 receptor-binding-domain (RBD) and the Spike glycoproteins of Delta, Omicron BA.1 and BA.4/5 and the common cold coronavirus HCoV-OC43. We also evaluated plasma capacity to neutralize authentic SARS-CoV-2 virus and to mediate Antibody-Dependent Cellular Cytotoxicity (ADCC). Most individuals mounted a strong antibody response against SARS-CoV-2 Spike. Plasma neutralization waned faster than anti-Spike binding and ADCC. We observed differences in humoral responses by age and circulating variants. Altogether, we show a global overview of antibody dynamics and functionality against SARS-CoV-2 in Cameroon.