Acute undifferentiated leukemia (AUL) is a rare subtype of leukemia that expresses no lineage-specific markers; no optimal treatment for AUL has been established. Here, we report a 16-year-old female with CD22-positive refractory AUL who responded well to inotuzumab ozogamicin (InO). Minimal residual disease negativity was achieved using InO, followed by HLA-mismatched unrelated bone marrow transplantation (BMT). Although grade II veno-occlusive disease/sinusoidal obstruction syndrome occurred, it improved immediately. She remained disease-free at 10 months post-BMT, without severe complications (grade III–IV). This case demonstrates the feasibility of a treatment strategy using InO against CD22-positive AUL.