Methotrexate (MTX) is widely used to manage autoimmune diseases such as rheumatoid arthritis, psoriasis, and eczema due to its anti-inflammatory and immunosuppressive properties. We present the case of a 69-year-old male individual with stage 3b chronic kidney disease (CKD) and diabetes mellitus, who developed acute MTX toxicity following a dosing error. The patient, prescribed MTX 7.5 mg weekly for chronic lower leg eczema, mistakenly took 5 mg every eight hours for four days. He presented with erythematous rashes, oral mucosal ulcerations, and pancytopenia, later diagnosed as neutropenic sepsis. Management included discontinuation of MTX, intravenous folinic acid, granulocyte-macrophage colony-stimulating factor (GM-CSF), and broad-spectrum antibiotics. By day 7, his blood counts and symptoms improved, and he was discharged on day 12. This case underscores the importance of patient education on proper MTX dosing to prevent life-threatening complications, particularly in high-risk populations such as the elderly and those with CKD.