The efficacy and safety of endoscopic submucosal dissection using a clutch cutter (ESD-CC) for subepithelial lesions within the esophagogastric submucosa (SELEGSM) has not been investigated. This study aimed to assess the efficacy and safety of ESD-CC for the treatment of SELEGSM. This prospective study included 15 consecutive patients with 18 SELEGSMs diagnosed by endoscopic ultrasonography. The primary outcomes were short-term outcomes including en bloc resection rate, R0 resection rate, procedure time, and complication rate. The secondary outcome was final histological diagnosis. Among the participants, 18 lesions were identified: 12 in the stomach (nine patients) and six in the esophagus (six patients). The en bloc resection rate was 94.4% (17/18). The R0 resection rate was 88.9% (16/18). The median operating time was 39 min, and no instances of perforation or bleeding were observed. The final diagnoses of SELEGSM included six neuroendocrine tumors (33.3%), six granular cell tumors (33.3%), two ectopic pancreases (11.1%), one inflammatory fibroid polyp (5.6%), one leiomyoma (5.6%), one lipoma (5.6%), and one leiomyosarcoma (5.6%). ESD-CC appears to be a technically efficient and safe approach for SELEGSM resection, suggesting its potential as a valuable treatment option.