Objective: To explore the role of lung ultrasound combined with multi-organ evaluation in assessing the risk of weaning from mechanical ventilation (MV) in severe patients. Methods: A retrospective analysis was conducted on 60 severe patients admitted to the hospital from December 2022 to December 2024, all of whom underwent MV treatment. Based on weaning status, thirty-eight patients were successfully weaned (success group), and 22 patients failed weaning (failure group). All patients underwent lung ultrasound and multi-organ evaluation. The parameter differences between the two groups were compared, risk factors for weaning risk were evaluated, and a receiver operating characteristic curve (ROC) was drawn to assess the predictive value of lung ultrasound combined with multi-organ evaluation for weaning risk. Results: The lung ultrasound score (LUS) of the success group was lower than that of the failure group, the left ventricular ejection fraction (LVEF) was higher than that of the failure group, and the diaphragmatic excursion (DE) and diaphragmatic thickening fraction (DTF) were higher than those of the failure group (P < 0.05). Multifactor analysis showed that LUS was a risk factor for weaning risk, while LVEF, DE, and DTF were protective factors (P < 0.05). The ROC showed that the area under the curve (AUC) of a single parameter for weaning risk was smaller than that of the combined parameters (P < 0.05). Conclusion: Lung ultrasound combined with multi-organ evaluation can predict the weaning risk of severe patients undergoing MV treatment, and the diagnostic efficiency of multiple parameters combined evaluation is higher.