In Zambia limited access to adequate water and sanitation is a key developmental challenge, particularly for rapidly expanding peri-urban areas. During 20162017, 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 factorssuch 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 waterthese 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.