In response to the significant public health threat caused by coronavirus disease (COVID-19), real-time surveillance, containment, and mitigation measures were implemented in the Federation of Bosnia and Herzegovina (FBiH). Our objective was to describe the surveillance methodology, response measures, and epidemiology of COVID-19 cases in FBiH from March 2020 to March 2022. The surveillance system implemented across FBiH enabled health authorities and the population to monitor the development of the epidemiological situation, the daily number of reported cases, as well as basic epidemiological characteristics and geographic distribution of cases. As of 31 March 2022, 249,495 cases of COVID-19, and a total of 8,845 deaths were recorded in FBiH. Upkeeping of real-time surveillance, maintaining non-pharmaceutical interventions, and speeding up the vaccination roll-out were paramount for controlling COVID-19 in FBiH.