Objective To observe the effect of transcranial ultrasound stimulation (TUS) on the recovery of upper limb motor function in stroke patients and explore its mechanism. Methods The inpatients with ischemic stroke and hemiplegia admitted to the Department of Rehabilitation Medicine of the Second Affiliated Hospital of Xi’an Jiaotong University between November 2019 and December 2021were prospectively included. The patients were randomly divided into a true stimulation group and a false stimulation group. All patients received routine medication treatment and rehabilitation training, with a course of 2 weeks. The patients in the true stimulation group also received TUS, and the stimulation site and mode in the false stimulation group were the same as those in the true stimulation group, but the transducer was in a non working mode. The changes in upper limb function and motor cortex electrical activity before and after treatment were compared between two groups of patients. The Wolf Motor Function Test (WMFT), Jebsen Hand Function Test (JHFT), and Fugl-Meyer Assessment-Upper Extremities (FMA-UE) were used as indicators of upper limb motor function. The motor evoked potential (MEP) latency, resting motor threshold (RMT), cortical silent period (CSP), and central motor conduction time (CMCT) were used as indicators of cortical excitability. Results A total of 30 patients were included, with 15 in the true stimulation group and 15 in the false stimulation group. There was no statistically significant difference in age, gender, course of disease, lesion side, handedness, National Institute of Health Stroke Scale score, and Barthel Index between the two groups of patients (P>0.05). Before treatment, there was no statistically significant difference in WMFT score, JHFT time, and FMA-UE score between the two groups of patients (P>0.05). After treatment, the WMFT score and FMA-UE score of both groups of patients increased compared to before treatment within the group, while the JHFT time decreased compared to before treatment within the group (P<0.05). The improvement degree of WMFT score (19.2±8.0 vs. 11.8±5.5), JHFT time [(39.3±20.4) vs. (26.0±15.9) s], and FMA-UE score [14.0 (12.0, 16.0) vs. 8.0 (7.0, 9.0)] before and after treatment in the true stimulation group were better than those in the false stimulation group (P<0.05). Before treatment, there was no statistically significant difference in MEP latency, CSP, CMCT, and RMT between the two groups of patients (P>0.05). After treatment, the MEP latency, CSP, CMCT, and RMT of both groups of patients decreased compared to before treatment within the group (P<0.05). The degree of decrease in CSP [(33.5±12.3) vs. (18.5±5.5) ms], CMCT [3.5 (2.5, 5.8) vs. 1.8 (1.5, 3.4) ms], and RMT [(19.2±12.8)% vs. (8.8±8.7)%] in the true stimulation group before and after treatment were greater than those in the false stimulation group (P<0.05). There was no statistically significant difference in the degree of decrease in MEP latency between the two groups before and after treatment (P>0.05). Both groups of patients had no adverse reactions during the treatment period. Conclusion TUS applied to the primary motor cortex can help restore upper limb motor function in stroke patients, and the mechanism of action may be related to TUS enhancing cortical excitability in the affected brain.