Background: This case-control study aimed to quantitatively assess the orbicularis oris muscle (OOM) in children with unilateral cleft lip and palate (UCLP) after primary lip repair using high-resolution ultrasonography, and to compare these measurements with children presenting isolated cleft palate (CP) without lip involvement. Methods: For this, 12 infants with UCLP who had undergone primary lip repair at 4–5 months of age were examined during subsequent palatoplasty at 9–12 months. They were compared to eight age-matched controls with isolated CP. Using a 22 MHz “hockey stick” transducer under general anaesthesia, muscle thickness (MT), height (MH), and cross-sectional area (CSA) of the OOM were measured on both sides of the upper lip. Results: The cleft side of the study group showed a significantly reduced CSA compared to the non-cleft side (p = 0.05), while MT was lower but not statistically significant. When compared with the control group, the cleft side showed significantly smaller CSA (p = 0.02) and MT (p = 0.05). No significant differences were observed between the non-cleft side and the control group, indicating normal muscle development on the unaffected side. Conclusions: Ultrasound proved to be a safe, reliable, and accessible tool for evaluating perioral muscle morphology in infants. The findings indicate persistent hypoplasia of the OOM on the cleft side post-repair, while the non-cleft side exhibits regular growth. These results may inform surgical technique selection and underline the potential of ultrasound for longitudinal studies. Future research could further enhance our understanding of muscle development and surgical outcomes in cleft patients.