Hemolytic uremic syndrome (HUS) is classically described as a triad of nonimmune hemolytic anemia, thrombocytopenia, and acute kidney injury. Atypical HUS (aHUS) is a rare variant of the disease, and it accounts for 5–10% of the cases. It has a poor prognosis, with a mortality rate exceeding 25% and a more than 50% chance of progressing into end-stage kidney disease (ESKD). Genetic or acquired dysregulation of the alternative complement pathway is highly implicated in the pathogenesis of aHUS. Multiple triggers for aHUS have been described in the literature, including pregnancy, transplantation, vaccination, and viral infections. Herein, we report a case of a previously healthy 38-year-old male who developed microangiopathic hemolytic anemia and severe kidney impairment one week after receiving the first dose of AstraZeneca SARS-CoV-2 vaccine. A diagnosis of aHUS was made after excluding other causes of thrombotic microangiopathies. Treatment with plasma exchange, prednisone, and rituximab (375 mg/m²) once weekly for four doses resulted in improvement of his hematological parameters. However, he progressed to ESKD.