Background: The prevalence of waterborne illnesses among students in rural and urban schools is a significant public health issue, especially in developing regions with limited access to clean water and sanitation. In Tanzania, research shows that rural populations still face significant challenges despite improved water access, impacting efforts to control waterborne diseases.

Objectives: This study assessed the prevalence of reported waterborne illnesses and their effects on students in rural and urban primary and secondary schools in Iringa, Tanzania.

Patients and Methods: This research, conducted from July 4 to July 25, 2024, used a quantitative cross-sectional analytical approach involving 1,536 students. Data were collected through structured questionnaires, and descriptive and comparative results were analyzed using the Statistical Package for the Social Sciences (SPSS) version 26. Significant associations were evaluated using P-values from cross-tabulation and further examined by binary logistic regression.

Results: The research found that 17.2% of rural school students suffer from waterborne illnesses, which is higher than the 10.9% prevalence seen in urban school students, both being a moderate prevalence. This study established a significant correlation in rural and urban schools through bivariate analysis (P < 0.05); however, binary logistic regression did not support this relationship.

Conclusion: Waterborne illness was more prevalent in rural than urban school students, although both face moderate reported prevalence. This necessitates attention to potential interventions, including equitable resource allocation, to close the rural-urban gap.