Abstract Background Data on risk factors for coronavirus disease 2019 (COVID-19)–associated hospitalization are needed to guide prevention efforts and clinical care. We sought to identify factors independently associated with COVID-19–associated hospitalizations. Methods Community-dwelling adults (aged ≥18 years) in the United States hospitalized with laboratory-confirmed COVID-19 during 1 March–23 June 2020 were identified from the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), a multistate surveillance system. To calculate hospitalization rates by age, sex, and race/ethnicity strata, COVID-NET data served as the numerator and Behavioral Risk Factor Surveillance System estimates served as the population denominator for characteristics of interest. Underlying medical conditions examined included hypertension, coronary artery disease, history of stroke, diabetes, obesity, severe obesity, chronic kidney disease, asthma, and chronic obstructive pulmonary disease. Generalized Poisson regression models were used to calculate adjusted rate ratios (aRRs) for hospitalization. Results Among 5416 adults, hospitalization rates (all reported as aRR 95% confidence interval) were higher among those with ≥3 underlying conditions (vs without) (5.0 3.9–6.3), severe obesity (4.4 3.4–5.7), chronic kidney disease (4.0 3.0–5.2), diabetes (3.2 2.5–4.1), obesity (2.9 2.3–3.5), hypertension (2.8 2.3–3.4), and asthma (1.4 1.1–1.7), after adjusting for age, sex, and race/ethnicity. Adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults aged ≥65 or 45–64 years (vs 18–44 years), males (vs females), and non-Hispanic black and other race/ethnicities (vs non-Hispanic whites). Conclusions Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions. Severe obesity, chronic kidney disease, diabetes, obesity, hypertension, asthma, age ≥45 years, male sex, and non-Hispanic black and other race/ethnicity are associated with increased risk of coronavirus disease 2019–associated hospitalizations.