Lip and palate deformities are an important craniofacial congenital anomaly that negatively affects the anatomy of the nasal cavity and maxilla. This study aimed to evaluate the nasal septum deviation in individuals with a unilateral cleft lip and palate. The sample consists of 22 unilateral cleft lip-palate patients and 20 controls with non-cleft skeletal Class III. Maximal septal deviation angle and linear dimension were measured on cone-beam computed tomography images. The localization of maximal septal deviation was determined. The data were analyzed and compared between unilateral cleft lip-palate patients and skeletal Class III individuals. For septal deviation, a significant discrepancy between unilateral cleft patients and skeletal Class III subjects was detected at the anterior nasal spine (ANS) level, the posterior nasal spine (PNS) level and the ANS-PNS midpoint level (p < 0.05). The maximum septal deviation angle of individuals with a unilateral cleft was significantly greater than individuals with skeletal Class III (p < 0.05). No statistically significant differences were found in the localization of maximum septal deviation between the unilateral cleft patients and the Class III individuals. Our results demonstrated that the maximum septal deviation angle and dimension had significant differences in individuals with a unilateral cleft, compared to a skeletal Class III control group. However, no statistically significant discrepancy was observed between three levels (ANS, PNS and ANS-PNS middle levels) in the unilateral cleft patients.