Children's of Mississippi at the University of Mississippi Medical Center serves as the state's only American Cleft Palate-Craniofacial Association-approved cleft team at the only pediatric hospital in the state. The goal of this study is to report geographic and demographic patterns of patients with orofacial cleft (OFC) treated at Children's of Mississippi, which are lacking. Patients with OFC treated at Children's of Mississippi from 2015 to 2020 were included. Demographic data were collected, including birth county and total live births from state data. Significant differences between incidence of OFC among public health regions of Mississippi were examined using analysis of variance (P < 0.05). Cases were compared with historical data from 1980 to 1989. There were 184 patients who presented with OFC, with a statewide incidence of 0.83 per 1000 live births among 222,819 live births in the state across 6 years. The incidence of OFC was 0.83/1000 for Whites and 0.82/1000 for non-Whites versus a historical rate of 1.36 and 0.54, respectively. Significantly fewer children in the northern region (0.25/1000) were born with OFC than in central (1.21; P < 0.001) and southern (0.86; P < 0.001) regions. Results from this study suggest changing regional patterns of OFC in Mississippi. Although rates increased among non-White infants, the overall incidence of OFC has decreased compared with historical data. The findings may reflect actual incidence patterns in the state or the proximity of certain regions to Children's of Mississippi. Further study may reveal regional differences in risk factors underlying OFC incidence, and/or issues with access to cleft care for different regions in the state.