Pyoderma gangrenosum (PG) is a rare inflammatory skin disease that is difficult to diagnose. PG may be an extra-intestinal manifestation of ulcerative colitis (UC). In recent times, coronavirus disease (COVID-19) vaccines have caused various adverse cutaneous reactions. However, to the best our knowledge, combinations thereof have not been reported. We encountered a case of PG triggered by COVID-19 vaccination in a patient with UC. A 40-year-old woman developed severe pain and an abscess in the dorsum of the left foot after receiving the first dose of the messenger RNA (mRNA)-based Pfizer/BioNTech BNT162b2 COVID-19 vaccine. Severe painful ulcers with purulent necrosis and gaseous gangrene progressed rapidly along the extensor tendons and muscles to the toes and ankle. Although surgical debridement can worsen PG by triggering pathergy, we nonetheless performed wide debridement including partial extensor tenotomy with abscess drainage to prevent progression to pyogenic ankle arthritis and to rescue the toes. Antibiotics, corticosteroids, and anticoagulants were prescribed during surgical wound management via negative pressure therapy. After the lesion improved, the skin and soft tissue defect were covered using a superficial circumflex iliac artery perforator free flap and a split-thickness skin graft. The patient was satisfied with the foot salvage, and could walk unaided (without a brace or cane) from 8 weeks after the final surgery. PG may be rare even in UC patients, but mRNA-based COVID-19 vaccines may find an immunosuppressive niche. A high level of caution and suspicion of skin manifestations after vaccination is essential.