Background: Disorders of gut–brain interaction (DGBI) are multifactorial. Early-life events are proposed as factors involved in their etiopathogenesis. The relationship between mode of delivery, prematurity, and DGBI development remains unclear. This study examines whether cesarean delivery and prematurity contribute to early childhood DGBI. Methods: Caregivers of children aged 1 month to 4 years from four Colombian cities participated in a cross-sectional study. Pediatricians completed the Spanish-validated Questionnaire of Pediatric Gastrointestinal Symptoms Rome IV (QPGS-IV). Data of children born by cesarean delivery and prematurity were compared with controls. Categorical data were analyzed using Fisher’s exact test, and odds ratios (ORs) with 95% confidence intervals (CIs). Results: DGBIs were identified in 26.6% of children, with functional constipation (FC) being the most prevalent (22.3%). Among children born via cesarean section (54.3%), 30.4% of them had a DGBI (OR = 1.54, 95% CI = 1.20–1.96, p = 0.00), and 26.3% had FC (OR = 1.67, 95% CI = 1.29–2.18, p = 0.00). Prematurity was observed in 12.6% of children and was associated with a higher prevalence of DGBI (35.7%, (OR = 1.64, 95% CI = 1.16–2.29, p = 0.00), with FC affecting 30.8% (OR = 1.66, 95% CI = 1.16–2.35, p = 0.00). Conclusions: Cesarean delivery and prematurity were found to be associated with DGBI in early childhood, particularly FC. These findings highlight the need for further research to explore potential mechanisms and confirm these associations.