Predictive scoring systems for adult patients receiving extracorporeal membrane oxygenation (ECMO) support for sepsis have not been yet reported. Based on the Chinese Society of ExtraCorporeal Life Support (CSECLS) Registry database, we conducted a retrospective observational study on adult patients supported with ECMO for sepsis (n = 465). On the basis of multivariable logistic regression analyses, four parameters at 24 h post-ECMO initiation (T₂₄) were identified as prognostic factors associated with in-hospital mortality: age, vasoactive inotropic score (VIS), partial pressure of oxygen in arterial blood (PaO₂), and lactate clearance. The sepsis-ECMO score was calculated based on these prognostic factors, which were converted into categorical variables. The area under the receiver operating characteristic curve for the sepsis-ECMO score was 0.704 (95% confidence interval [CI]: 0.658–0.751). Four risk classes, namely class Ⅰ (score 0), class Ⅱ (score 5), class Ⅲ (score 6–10), and class Ⅳ (score ≥ 11), were identified according to sepsis-ECMO score quartiles. Patients in the lower sepsis-ECMO score classes had significantly better survival than those in the higher classes (log-rank test, p < 0.001). The sepsis-ECMO score may help in the risk stratification of patients, facilitate the communication of objective prognostic information, and provide a clearer direction for shared decision-making.