In Zambia limited access to adequate water and sanitation is a key developmental challenge, particularly for rapidly expanding peri-urban areas. During 2016–2017, a cross-sectional household survey was conducted among 12,500 households representing ~60,000 individuals to assess the burden of household diarrheal and respiratory disease and to measure water, sanitation, and hygiene (WASH) characteristics in Lusaka, Zambia. We found that socio-economic factors, including having an additional household member, having children <5 years old in the household, living in a rental home, and higher annual household expenditure were associated with diarrhea and respiratory illness. We also found an increased risk for diarrhea associated with a number of WASH-related factors–such as not covering all water storage containers, not using soap for handwashing, having an unimproved sanitation facility, and utilizing a heavily shared toilet (≥18 people). Detectable free chlorine residual in household stored water and more hours of water availability per day were associated with reduced odds of waterborne illness. In all, 75% of household stored water was contaminated with E. coli and households consuming less water (<20 L/day per person) for all purposes had lower odds of diarrhea than households consuming more water—these findings highlight the need for enhanced WASH services within densely populated peri-urban areas and the importance of achieving universal access to safely managed water and sanitation services.