<jats:p>Abstract Objectives Our aim was to examine the geographic, socio-economic and behavioural factors associated with disease and antibiotic consumption in Nepal from 2006 to 2016; as well as explore healthcare seeking patterns and the source of antibiotics. Methods Cross-sectional data on children under five in households from Nepal was extracted from the 2006, 2011 and 2016 Demographic Health Surveys (DHS). Univariate and multivariate analyses were carried out to assess the association of disease prevalence and antibiotic use with age, sex, ecological zone, urban/rural location, wealth index, maternal smoking, use of clean fuel, sanitation, nutrition, access to healthcare and vaccinations. Results Prevalence of fever, acute respiratory infection (ARI) and diarrhoea decreased from 2006 to 2016, while the proportion using antibiotics increased. Wealth, use of clean fuel, improved toilet sanitation, nutrition and access to healthcare were associated with reduced rates of disease. Those in the highest wealth index are starting to use less antibiotics and antibiotic consumption in rural areas has surpassed urban regions over time. Health-seeking from the private sector has overtaken government facilities since 2006 with source of antibiotics mainly originating from pharmacies and private hospitals. Adherence to WHO recommended antibiotics has reduced over time. Conclusions With rising wealth, there has been decline in disease prevalence but increase in antibiotic use with greater access to unregulated sources. Understanding antibiotic use and identifying associated behavioural and socio-economic factors could help to inform methods in reducing inappropriate antibiotic use whilst ensuring access to those who need them.</jats:p>