There have been observed racial differences in the rates of SARS-CoV-2 infection, hospitalization, and multisystem inflammatory syndrome in children (MIS-C). These studies, however, have been incomplete since they have relied on passive reporting, statistics on catchment populations, and infection prevalence that are unclear. Using active surveillance based on the seroprevalence-based cumulative incidence of pediatric SARS-CoV-2 infection in a defined catchment area of 16 counties in Mississippi, researchers sought to characterize the population-based incidence of MIS-C and COVID-19 hospitalizations among non-Hispanic Black and White children. From March 2020 through February 2021, physicians at the University of Mississippi Medical Center, the state’s primary pediatric referral facility, actively monitored the hospital population for cases of MIS-C and acute COVID-19 that met clinical and laboratory criteria. The estimated seroprevalence of SARS-CoV-2 in the population, broken down by race, was derived from a convenience sample of people aged less than 18 years.  Among children’s 74 acute COVID-19 hospitalizations, 38 were diagnosed as MIS-C. In comparison to White children, Black children had a cumulative incidence of MIS-C that was 4.7% higher (40.7 versus 8.3 cases per 100,000 SARS-CoV-2 infections). Among Black children, the hospitalization rate due to COVID-19 was 62.3 per 100,000 SARS-CoV-2 infections, while among White children, it was 33.1. The results demonstrate a strikingly higher incidence of SARS-CoV-2-hospitalization and MIS-C in non-Hispanic Black children compared to White children before the introduction of COVID-19 vaccination in children, based on data from the same catchment area, active surveillance, and cumulative incidence of infection estimated by seroprevalence. No evidence suggests that differences in exposure or testing are to blame for the observed SARS-CoV-2 symptomatology variation. Targeted vaccination treatments will reduce inequalities in SARS-CoV-2 symptoms in children.