Introduction Household food insecurity and inadequate water, sanitation, and hygiene (WASH) contribute to ill health. However, the interactions between household food insecurity, WASH and health have been rarely assessed concurrently. This study investigated compounded impacts of household food insecurity and WASH on self-reported physical and mental health of adults in the Vietnamese Mekong Delta. Materials and methods This cross-sectional survey interviewed 552 households in one northern and one southern province of the Vietnamese Mekong Delta. The survey incorporated previously validated tools such as the Short Form 12-item Health Survey, Household Food Insecurity Assessment Scale, and the Access and Behavioural Outcome Indicators for Water, Sanitation, and Hygiene. Physical and mental health were quantified using the physical health composite score (PCS) and mental health composite score (MCS), respectively. These measures were the dependent variables of interest for this study. Results Statistical analysis revealed that household food insecurity and using <50 litres of water per person per day (pppd) were independently associated with lower PCS (p<0.05), after adjusting for socio-economic confounders. Household food insecurity and lack of food availability, using <50 litres of water pppd, and the use of untreated drinking water were associated with lower MCS (p<0.05), with water usage being an effect modifier of the relationship between household food insecurity and MCS. The results indicate that being food insecure and having limited potable quality water had a compounding effect on MCS, compared to being individually either food insecure or having limited water. Conclusion This study is one of only a few that have established a link between potable water availability, food insecurity and poorer physical and mental health. The results also indicate a need to validate national data with fine-scale investigations in less populous regions to evaluate national initiatives with local populations that may be at higher risk. Adopting joint dual-action policies for interventions that simultaneously address water and food insecurity should result in larger improvements in health, particularly mental health, compared to targeting either food or water insecurity in isolation.