Background/Objectives: Prediction of a difficult airway during pre-anesthetic evaluation is of great importance because it enables an adequate anesthetic approach and airway management. As there is a scarcity of prospective studies evaluating the role of anthropometric measures of the face and neck in predicting difficult airways in infants with an apparently normal airway, we aimed to identify the aforementioned predictors of difficult facemask ventilation and intubation in infants. Methods: A prospective, observational study that included 97 infants requiring general endotracheal anesthesia was conducted. Anthropometric and specific facial measurements were obtained before ventilation and intubation. Results: The incidence of difficult facemask ventilation was 15.5% and 38.1% for difficult intubation. SMD (sternomental distance), TMA (tragus-to-mouth angle distance), NL (neck length) and mouth opening were significantly lower in the difficult facemask ventilation group. HMDn (hyomental distance in neutral head position), HMDe (hyomental distance in neck extension), TMD (thyromental distance), SMD, mandibular development and mouth opening were significantly different in the intubation difficulty group compared to the non-difficult group. HMDn and HMDe showed significantly greater specificities for difficult intubation (83.8% and 76.7%, respectively), while higher sensitivities were observed in TMD, SMD and RHSMD (ratio of height to SMD) (89.2%, 75.7%, and 70.3%, respectively). Regarding difficult facemask ventilation, TMA showed greater sensitivity (86.7%) and SMD showed greater specificity (80%) compared to other anthropometric parameters. In a multivariate model, BMI (body mass index), COPUR (Colorado Pediatric Airway Score), BOV (best oropharyngeal view) and TMA were found to be independent predictors of difficult intubation, while BMI, ASA (The American Society Physical Status Classification System), CL (Cormack–Lehane Score), TMA and SMD predicted difficult facemask ventilation. Conclusions: Preoperative airway assessment is of great importance for ventilation and intubation. Patient’s overall condition and facial measurements can be used as predictors of difficult intubation and ventilation.