Background and Objective Since exacerbation of chronic obstructive pulmonary disease (ECOPD) is both common and often fatal, accurate prognostication of patients hospitalized for ECOPD is critical. We aimed to develop and validate a new score for predicting hospital mortality. Methods Independent predictors of in-hospital mortality were identified from a large prospective cohort of ECOPD from 10 medical centers in China between September 2017 and July 2021, and incorporated into a clinical prediction score. Application of this score was then prospectively evaluated in an external validation cohort. The prognostic value of the scores was assessed by the area under the receiver operating characteristic curve (AUC). Results A total of 14,007 patients were included in the derivation cohort, and 201 patients (1.43%) died in the hospital. The 11 strongest independent predictors were combined to form the Chronic Heart failure, Age >= 75, altered Mental status, Pneumonia, Interstitial lung disease, diastolic blOod pressure <= 70 mmHg, Neutrophil ratio > 85 (%), Anemia, Long-term bed rest, hEart Rate > 100 (beats/minute), and blood urea niTrogen > 7.3 mmol/L, CHAMPION-ALERT Score, which enabled patients to be stratified according to increasing risk of in-hospital mortality: score 0-5, 0.3%; score 6-9, 4.4%; score 10-16, 25.9%. The score displayed excellent predictive value for mortality with an AUC of 0.89 (95% CI 0.87-0.92), which was reproduced in the validation cohort of 3048 patients. The discrimination of the new score was superior to or comparable to that of existing prognostic scores (DECAF, BAP-65, and CURB-65). Conclusion A new scoring system composes of 11 routinely available clinical variables on admission can accurately predict in-hospital mortality in ECOPD and shows a trend toward better performance compared to previous prognostic scores.