Individuals with nonsyndromic cleft lip with or without cleft palate (CL/P) have altered brain structure compared with healthy controls. Preliminary evidence suggests that the corpus callosum may be dysmorphic in orofacial clefting; however, this midline brain structure has not been systematically assessed in this population. The goal of the present study was to carry out a morphometric assessment of the corpus callosum and its relationship to cognitive performance in a well-characterized patient cohort with orofacial cleft. Midline brain images were obtained from previously collected MRI scans of 24 CL/P subjects and 40-adult-male controls. Eight landmarks on the corpus callosum were digitized on each image and their x,y coordinate locations saved. A geometric morphometrics analysis was applied to the landmark coordinate data to test for shape differences across groups. The relationship between corpus callosum shape and IQ was explored with nonparametric correlation coefficients. Results revealed significant differences in mean corpus callosum shape between CL/P cases and controls (P = 0.029). The CL/P corpus callosum was characterized by increased overall convexity resulting from a superior and posterior displacement. Within CL/P cases, increased corpus callosum shape dysmorphology was moderately correlated with reduced performance IQ (r = 0.546). These results provide additional evidence that midline brain changes may be an important part of the orofacial cleft phenotype. © 2013 Wiley Periodicals, Inc.