Discrepancies in prevalence among infants with orofacial clefts are public health research priorities. Our objective was to calculate updated estimated prevalence of orofacial clefts in the United States, with sub-analyses by racial/ethnic group. The National Birth Defect Prevention Network database was used to evaluate trends in cases with orofacial cleft in the United States from 2006 to 2018. Cases with cleft lip with and without cleft palate (CL ± P) and cleft palate (CP) alone were sub-stratified by racial/ethnic category. Estimated prevalence was calculated using the total live births reported in each maternal racial/ethnic group. The odds ratio (OR) was calculated to measure the strength of association between racial/ethnic group and risk of orofacial clefts. Estimated prevalence rates show that maternally-reported Native American/Alaskan Native individuals were 43.8% (p < 0.0001) and 36.0% (p < 0.0001) more likely to have CL ± P and CP alone, respectively, compared to maternally-reported non-Hispanic White individuals. Estimated prevalence of CL ± P in maternally-reported non-Hispanic Black individuals (OR = 0.64) and maternally-reported Asians/Pacific Islander individuals were significantly lower than in maternally-reported non-Hispanic White individuals (OR = 0.63, p < 0.0001). Estimated prevalence of CP alone was significantly lower in maternally-reported non-Hispanic Black individuals (OR = 0.64, p < 0.0001), maternally-reported Asians/Pacific Islander individuals (OR = 0.69, p < 0.0001), and maternally-reported Hispanic individuals (OR = 0.81, p < 0.0001). Across the total population, there was no significant change in estimated orofacial cleft prevalence. However, there were significant disproportions in estimated orofacial cleft prevalence across racial/ethnic groups, which may guide further discussion among craniofacial health care providers and centers and their patients regarding differences in cleft risk factors.