A 39-year-old man with a 5-year history of ileocolonic Crohn's disease received treatment with 6-mercaptopurine and adalimumab. A computed tomography scan was performed due to a persistent cough, revealing esophageal wall thickening. Esophagogastroduodenoscopy identified multiple longitudinal ulcers throughout the esophagus. Despite infliximab treatment, the esophageal lesions deteriorated, leading to the initiation of upadacitinib for antitumor necrosis factor-refractory esophageal lesions. Consequently, all esophageal lesions were healed, and serum biomarkers returned negative results. Although upadacitinib is effective for patients with ileocolonic Crohn's disease, this is the first case demonstrating its efficacy for refractory esophageal lesions.