Objective To investigate the clinical validation of diaphragmatic ultrasound indicators for early diagnosis of intensive care unit-acquired weakness (ICU-AW). Methods A total of 100 ICU-AW patients admitted to Luoyang Central Hospital from January 2023 to January 2025 were selected as the study group, and another 100 healthy individuals undergoing physical examinations during the same period were selected as the control group. All subjects underwent ultrasonographic diaphragmatic assessment. Differences in ultrasound-derived diaphragmatic parameters were compared between the two groups, and their clinical diagnostic efficacy for ICU-AW was analyzed. Results The levels of diaphragm thickness at end expiration (DTee), diaphragm thickness at end inspiration (DTei) and diaphragm thickness at end inspiration (DTei) in the study group were lower than those in the control group (all P＜0.05). Multivariate Logistic regression analysis showed that DTee, DTei, and DTF were protective factors for ICUAW (all P＜0.05). The receiver operator characteristic (ROC) curve results showed that the area under the curve (AUC) of DTee, DTei, and DTF for diagnosing ICU-AW were 0.969, 0.902, and 0.902, respectively, indicating good diagnostic efficacy. Conclusion Diaphragmatic ultrasound parameters DTee, DTei, and DTF have high clinical value in the early diagnosis of ICU-AW and can serve as sensitive biological indicators for early identification of the disease.