Background: Cryptogenic multifocal ulcerating stenosing enteritis (CMUSE) is a rare idiopathic small-bowel disorder characterised by recurrent mucosal ulceration and multifocal strictures, often leading to mechanical obstruction and repeated surgical intervention. It presents significant diagnostic challenges, particularly in distinguishing it from Crohn’s disease, coeliac disease, and drug-induced enteropathy. Case Presentation: We report a 44-year-old man with Down syndrome and a background of Hirschsprung’s disease, coeliac disease, and multiple prior abdominal surgeries, who developed recurrent small-bowel obstruction due to multifocal strictures of uncertain aetiology. He experienced progressive obstructive episodes requiring repeated hospitalisations. Initial management included endoscopic assessment and jejunal dilatation; however, disease progression rendered endoscopic therapy ineffective. The patient subsequently underwent exploratory laparotomy with small-bowel resection with or without stricturoplasty, and gastrojejunostomy where indicated, to relieve obstruction and obtain full-thickness tissue for diagnosis. Despite multiple resections, stricturing disease recurred. Extensive radiological, serological, endoscopic and histological evaluation excluded Crohn’s disease, active coeliac enteropathy, infectious, vasculitic, and drug-related causes. The presence of multifocal ulceration, mucosa-predominant strictures, and non-transmural inflammation supported a diagnosis of CMUSE. The clinical course was complicated by wound dehiscence, intra-abdominal sepsis, and enterocutaneous fistula, requiring prolonged multidisciplinary management. Conclusion: CMUSE is a rare but important differential diagnosis in patients with recurrent small-bowel strictures mimicking Crohn’s disease. Recognition is essential to avoid inappropriate immunosuppression and cumulative operative morbidity, and management requires a coordinated multidisciplinary approach.