Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, characterized by the presence of ulcers and potential extraintestinal symptoms. Approximately 20% of UC patients may progress to acute severe ulcerative colitis (ASUC), a serious condition marked by resistance to conventional treatment methods. Prompt and intensive treatment for ASUC is essential to prevent adverse outcomes. The primary therapeutic approach typically involves intravenous corticosteroids; however, when this is ineffective, biological agents such as infliximab or immunosuppressants like cyclosporine are necessary. Upadacitinib, a Janus kinase (JAK) inhibitor, is approved for the treatment of moderate to severe UC in adult patients. However, its safety and efficacy for ASUC have not yet been established. For ASUC patients previously treated with infliximab, treatment options are limited, underscoring the need for new approaches to improve patient outcomes. JAK inhibitors could play a crucial role in this regard. This case report discusses a 40-year-old male with UC unresponsive to therapy for two years, who was treated with upadacitinib. The patient demonstrated clinical and endoscopic improvement within one week of initiating upadacitinib, indicating the drug’s potential effectiveness in this challenging clinical context.