Although the coronavirus disease (COVID-19) emergency status is easing, the COVID-19 pandemic continues to affect healthcare systems globally. It is crucial to have a reliable and population-wide prediction tool for estimating COVID-19-induced hospital admissions. We evaluated the feasibility of using wastewater-based epidemiology (WBE) to predict COVID-19-induced weekly new hospitalizations in 159 counties across 45 states in the United States of America (USA), covering a population of nearly 100 million. Using county-level weekly wastewater surveillance data (over 20 months), WBE-based models were established through the random forest algorithm. WBE-based models accurately predicted the county-level weekly new admissions, allowing a preparation window of 1-4 weeks. In real applications, periodically updated WBE-based models showed good accuracy and transferability, with mean absolute error within 4-6 patients/100k population for upcoming weekly new hospitalization numbers. Our study demonstrated the potential of using WBE as an effective method to provide early warnings for healthcare systems.