The incidence of meningococcal disease has declined steadily in the U.S. since a peak of reported disease in the late 1990s. Even before routine use of a meningococcal conjugate vaccine against serogroups A, C, W, and Y (MenACWY) was recommended for adolescents in 2005, the overall annual incidence of meningococcal disease had decreased 64%, from 1.1 cases per 100,000 population in 1996 to 0.4 cases per 100,000 population in 2005. In 2021, the rate of meningococcal disease in the United States reached a historic low of 0.06 cases per 100,000 population.

In 2021, the most recent CDC surveillance final report stated that, of U.S. cases with known serogroup, 46 cases were serogroup B (incidence rate of 0.01 cases per 100,000, or 1 case per 10 million population) and 108 cases were serogroups C, Y, or W. The incidence of disease is extremely low in all age groups, but is highest in infants under 1 year (0.56 cases per 100,000), children age 1 through 4 years (0.10 cases per 100,000). Among adolescents age 16–23, the incidence rate was 0.05 cases per 100,000 population, which equals 5 cases per 10 million people age 16–23 in 2021. In total, 209 cases of meningococcal disease were reported in the United States in 2021.

Rates of meningococcal disease in the United States increased in 2023. Much of this increase was due to a sharp increase in serogroup Y disease. In 2023, 415 confirmed and probable meningococcal disease cases were reported in the United States (preliminary data), which is similar to the rate in 2014. People disproportionately affected by the increase include Black people between the ages of 30 and 60 years, and adults with HIV. Adults with HIV are routinely recommended to be vaccinated against meningococcal serogroups A, C, W, and Y.