Estimation of human water withdrawals is more important now than ever due to uncertain water supplies, population growth, and climate change. Fourteen percent of the total water withdrawal in the United States is used for public supply, typically including deliveries to domestic, commercial, and occasionally including industrial, irrigation, and thermoelectric water withdrawal. Stewards of water resources in the USA require estimates of water withdrawals to manage and plan for future demands and sustainable water supplies. This study compiled the most comprehensive conterminous United States water withdrawal data set to date and developed a machine learning framework for estimating public supply withdrawals and associated uncertainty for the period 2000–2020. The modeling approach provides service area resolution estimates to allow for annual and monthly water withdrawal estimation while incorporating a complex array of driving factors that include hydroclimatic, demographic, socioeconomic, geographic, and land use factors. Model results reveal highly variable and lognormally distributed per‐capita water withdrawal, spanning from 30 to 650 gallons per capita per day (GPCD), across community, regional, and national scales, with pronounced seasonal variations. Analysis of estimated withdrawal trends indicates that the national annual average withdrawal experienced a decline at a rate of 0.58 GPCD/year during the period from 2000 to 2020. Model interpretation reveals a complex interplay between public supply withdrawal and key predictors, including population size, warm‐season precipitation, counts of large buildings and houses, and areas of urban and commercial land use. The developed models can forecast future public supply driven by various climate, demographic, and socioeconomic scenarios.