Abstract Background In Belgium, the first COVID-19 death was reported on 10 March 2020. Nursing home (NH) residents are particularly vulnerable for COVID-19, making it essential to follow-up the spread of COVID-19 in this setting. This manuscript describes the methodology of surveillance and epidemiology of COVID-19 cases, hospitalizations and deaths in Belgian NHs. Methods A COVID-19 surveillance in all Belgian NHs (n = 1542) was set up by the regional health authorities and Sciensano. Aggregated data on possible/confirmed COVID-19 cases and hospitalizations and case-based data on deaths were reported by NHs at least once a week. The study period covered April–December 2020. Weekly incidence/prevalence data were calculated per 1000 residents or staff members. Results This surveillance has been launched within 14 days after the first COVID-19 death in Belgium. Automatic data cleaning was installed using different validation rules. More than 99% of NHs participated at least once, with a median weekly participation rate of 95%. The cumulative incidence of possible/confirmed COVID-19 cases among residents was 206/1000 in the first wave and 367/1000 in the second wave. Most NHs (82%) reported cases in both waves and 74% registered ≥10 possible/confirmed cases among residents at one point in time. In 51% of NHs, at least 10% of staff was absent due to COVID-19 at one point. Between 11 March 2020 and 3 January 2021, 11,329 COVID-19 deaths among NH residents were reported, comprising 57% of all COVID-19 deaths in Belgium in that period. Conclusions This surveillance was crucial in mapping COVID-19 in this vulnerable setting and guiding public health interventions, despite limitations of aggregated data and necessary changes in protocol over time. Belgian NHs were severely hit by COVID-19 with many fatal cases. The measure of not allowing visitors, implemented in the beginning of the pandemic, could not avoid the spread of SARS-CoV-2 in the NHs during the first wave. The virus was probably often introduced by staff. Once the virus was introduced, it was difficult to prevent healthcare-associated outbreaks. Although, in contrast to the first wave, personal protective equipment was available in the second wave, again a high number of cases were reported.