A 20-year-old woman with ileocolonic, stricturing, and penetrating Crohn's disease (CD) presented with new onset perianal and vulvar CD despite having a diverting ileostomy and medical therapy with ustekinumab. She had previous secondary nonresponse to infliximab, vedolizumab, and adalimumab. There is a paucity of data supporting the use of medical therapies for perianal CD. Upadacitinib is approved for treatment of moderate to severely active ulcerative colitis and CD. This case demonstrates successful and rapid resolution of perianal CD within weeks of initiating upadacitinib.