INTRODUCTION: Acute severe ulcerative colitis (ASUC) represents a medical emergency associated with high mortality and morbidity. While corticosteroids are the primary treatment, cases that are unresponsive often require rescue therapy with either infliximab or cyclosporine to reduce the rate of colectomy. Janus kinase inhibitors, such as tofacitinib and upadacitinib, are a highly efficacious therapy with rapid induction of clinical response in moderate to severe ulcerative colitis (UC). Limited data are available on its use on ASUC. We present the first case utilizing upadacitinib as sequential medical rescue therapy in ASUC as well as intestinal ultrasound as a useful tool for disease and response monitoring. CASE PRESENTATION: A 69-year-old female who presented with corticosteroid-refractory ASUC partially responded to dose-intensified infliximab and finally achieved clinical remission with upadacitinib. This resulted in swift clinical remission and significant improvement in her mucosal inflammation on intestinal ultrasound. CONCLUSION: This successful intervention not only avoided colectomy but demonstrated sustained clinical and sonographic remission 16 weeks of post-treatment. Upadacitinib, with its rapid action and efficacy, shows promise in ASUC and should be supported by registration trials and real-world studies. Despite successful outcomes in this case, further validation and long-term data are necessary.