Objective To explore the predictive value of lung ultrasound B-line score combined with diaphragm function-related parameters for weaning from severe mechanical ventilation patients. Methods A total of one hundred and fifteen critically ill mechanically ventilated patients admitted to our hospital from April 2021 to August 2023 were selected. Patients’ readiness for weaning was assessed through lung ultrasonography with a calculated B-line score， and spontaneous breathing trials （SBT） with a T-tube pressure support. The indicators of right diaphragmatic excursion and thickness were determined by bedside ultrasound at 30 min of SBT. The diaphragm rapid shallow breathing index， diaphragmatic excursion， and thickness were recorded. Patients were divided into the success group （n = 78） and the failure group （n = 37） based on their respiratory status 48 hours after weaning. The clinical data were collected， multivariate Logistic regression was used to identify factors affecting the successful weaning in critically ill mechanically ventilated patients， and receiver operating characteristic curve （ROC） was plotted to evaluate the predictive value of lung ultrasound B-line score combined with diaphragm function-related parameters for weaning in critically ill mechanically ventilated patients. Results The failure group reported a larger B-line score and diaphragm rapid shallow breathing index， and a smaller changes in diaphragmatic excursion and thickness compared to the success group （P < 0.05）. The Acute Physiology and Chronic Health Evaluation Ⅱ（APACHE-Ⅱ）， Sequential Organ Failure Assessment （SOFA） score， respiratory rate， and shallow breathing index were notably higher in the failure group than in the success group， the duration of mechanical ventilation was less than that of the weaning success group （P < 0.05）. Logistic regression analysis denoted that lung ultrasound B-line score， diaphragmatic rapid shallow breathing index， right diaphragmatic excursion， diaphragmatic thickness， APACHE-Ⅱscore， SOFA score， respiratory rate， and rapid shallow breathing index were important factors for successful weaning in critically ill mechanically ventilated patients （P < 0.05）. ROC curve indicated that the area under the curve （AUC） of combined test of lung ultrasound B-line score， diaphragmatic rapid shallow breathing index， right diaphragmatic excursion， and diaphragmatic thickness for weaning in critically ill mechanically ventilated patients was 0.931， which was larger than separate test （P < 0.05）. Conclusion Lung ultrasound B-line score combined with diaphragm function-related parameters has a high predictive value for weaning in critically ill mechanically ventilated patients.