Background Globally, research on oral and maxillofacial lesions among newborns and infants remains limited. Aim To describe demographic patterns, histopathological findings, and locations of oral and maxillofacial lesions in newborns (birth‐1 month) and infants (>1 month‐2 years) reported over 51 years. Design A retrospective cross‐sectional study on histopathological records of newborns and infants was conducted. Patients’ demographic characteristics (age, gender, and race), histopathological diagnosis, and lesion's location were gathered. Pearson's chi‐square or Fisher's exact test was performed to determine associations between demographic characteristics and different categories of lesions. Results Out of 66,546 specimens received, 0.44% (290 specimens) were from patients aged 2 years and younger (27 newborns and 263 infants). The most common category was inflammatory/reactive (44.2%), followed by tumour/tumour‐like (42.0%), cystic/pseudocystic (6.6%), and miscellaneous lesions (5.5%). Mucous extravasation cysts (23.4%) and Langerhans cell histiocytosis (7.2%) were the most common histopathological diagnoses. Tumour/tumour‐like lesions were significant in newborns (P = .021), and majority were congenital epulis (40.7%). Inflammatory/reactive lesions were significantly higher in male (P = .025) and infants (P = <.001) with predominant incidences of mucous extravasation cysts (24.7%). There was a more than one ten probability of malignant lesions (11.4%). Conclusion Routine clinical head and neck examinations in newborns and infants are the key to early detection of lesions.