Water remains a significant player in spreading pathogens, including those associated with neglected tropical diseases. The implications of socio-demographic delineations of water quality, sanitation, and hygiene (“WASH”) interventions are on the downswing. This study assessed waterborne diseases and perceived associated WASH factors in the Bushenyi and Sheema districts of South-Western Uganda. This study examines the linear relationship between WASH and identifies the association of specific demographic factors as well as their contributions/correlations to waterborne disease in the study area. A structured qualitative and quantitative data collection approach was adopted in face-to-face questionnaire-guided interviews of 200 respondents on eight surface water usage. Most participants, 65.5%, were females and had a higher score of knowledge of WASH (71%), 68% score on the improper practice of WASH, and 64% score on unsafe water quality. Low score for basic economic status was (57%), report of common diarrhoea was (47%), and a low incidence of waterborne disease outbreaks (27%). The principal component analysis (PCA) depicts the knowledge and practice of WASH to have a strong positive correlation (r= 0.84,p< 0.001;r= 0.82,p< 0.001); also economic status positively correlated with grade of water source, knowledge, and practice of WASH (correlation coefficient = 0.72; 0.99; 0.76 andp-values = 0.001; < 0.001; < 0.001 respectively). Occupation (p= 0.0001,OR= 6.798) was significantly associated with knowledge and practice of WASH, while age (r= −0.21,p< 0.001) was negatively associated with knowledge and practice of WASH. The basic economic status explains why “low economic population groups” in the remote villages may not effectively implement WASH, and diarrhoea was common among the population. Diarrhoea associated with unsafe water quality and improper practice of WASH is common among the study population, and there is a low incidence of waterborne disease outbreaks. Therefore, government, stakeholders, and non-governmental organisations should work together to promote proper practice of WASH conditions to limit the occurrence of diarrhoea and prevent potential waterborne disease outbreaks.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10661-023-11270-1.