Objective: To explore the risk factors of acquired weakness in ICU patients and construct a prediction model. Methods: Using convenience sampling method, 245 intensive care patients admitted to ICUs of three tertiary hospitals in Shiyan City from March 2022 to April 2023 were selected, of which 172 cases from March to December 2022 were used as the modeling group and 73 cases from January to April 2023 were used as the validation group. The predictive effect of the model was examined using the area under the curve (AUC) of the receiver operating characteristic curve (ROC) and Hosmer-Lemeshow goodness-of-fit, and the model column line graph was plotted. Results: The incidence of ICU-acquired weakness was 36.63% (63/172) and 38.37% (28/73) in the modeling and validation groups, respectively. Patient’s history of alcohol consumption, mode of admission to the ICU, treatment with CRRT, mechanical ventilation, restraint braking, use of analgesics, use of norepinephrine, use of glucocorticoids, and length of stay in the ICU were the independent influencing factors of acquired weakness in ICU patients (p < 0.05). The AUCs of the modeling and validation groups were 0.979 and 0.887, respectively. Conclusion: The risk prediction model constructed in this study can predict the risk of acquired weakness in ICU, which can provide a reference for healthcare professionals to formulate interventions at an early stage.