Importance The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented stress on health systems across the world, and reliable estimates of risk for adverse hospital outcomes are needed. Objective To quantify admission laboratory and comorbidity features associated with critical illness and mortality risk across 6 Eastern Massachusetts hospitals. Design, Setting, and Participants Retrospective cohort study of all individuals admitted to the hospital who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction across these 6 hospitals through June 5, 2020, using hospital course, prior diagnoses, and laboratory values in emergency department and inpatient settings from 2 academic medical centers and 4 community hospitals. The data were extracted on June 11, 2020, and the analysis was conducted from June to July 2020. Exposures SARS-CoV-2. Main Outcomes and Measures Severe illness defined by admission to intensive care unit, mechanical ventilation, or death. Results Of 2511 hospitalized individuals who tested positive for SARS-CoV-2 (of whom 50.9% were male, 53.9% White, and 27.0% Hispanic, with a mean [SD ]age of 62.6 [19.0] years), 215 (8.6%) were admitted to the intensive care unit, 164 (6.5%) required mechanical ventilation, and 292 (11.6%) died. L1-regression models developed in 3 of these hospitals yielded an area under the receiver operating characteristic curve of 0.807 for severe illness and 0.847 for mortality in the 3 held-out hospitals. In total, 212 of 292 deaths (72.6%) occurred in the highest-risk mortality quintile. Conclusions and Relevance In this cohort, specific admission laboratory studies in concert with sociodemographic features and prior diagnosis facilitated risk stratification among individuals hospitalized for COVID-19. Question How well can sociodemographic features, laboratory values, and comorbidities of individuals hospitalized with coronavirus disease 2019 (COVID-19) in Eastern Massachusetts through June 5, 2020, predict a severe illness course? Findings In this cohort study of 2511 hospitalized individuals positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction who were admitted to 1 of 6 hospitals, 215 (8.6%) were admitted to the instensive care unit, 164 (6.5%) required mechanical ventilation, and 292 (11.6%) died. In a risk prediction model, 212 deaths (78%) occurred in the top mortality-risk quintile. Meaning Simple prediction models may assist in risk stratification among hospitalized patients with COVID-19. This cohort study assesses admission laboratory and comorbidity features associated with critical illness and mortality risk among patients hospitalized with coronavirus disease 2019 (COVID-19) across 6 Eastern Massachusetts hospitals.