Background Stromal-cell-derived factor 1 (SDF-1) plays a crucial role in hematopoiesis and has been implicated in acute myeloid leukemia (AML) pathogenesis. Understanding its relationship with chemotherapy outcomes could lead to improved therapeutic approaches for elderly AML patients. Methods This study retrospectively analyzed the medical records of elderly AML patients (n = 187) and compared serum SDF-1 alpha levels with age-matched controls (n = 120). Patients received CAG (cytarabine, aclarubicin, and G-CSF)-based chemotherapy, and serum SDF-1 alpha levels were assessed using ELISA. Results Serum SDF-1 alpha levels were significantly elevated in elderly AML patients compared to controls (p < 0.001). Receiver operating characteristic (ROC) analysis confirmed its diagnostic relevance, revealing the area under the ROC curve (AUC) of 0.76. Factors such as age, French-American-British (FAB) classification, Eastern Cooperative Oncology Group (ECOG) performance status, primary AML status, white blood cell count, and bone marrow blast cell ratio, were confirmed to be prognostically relevant. Serum SDF-1 alpha levels were elevated in patients who did not achieve complete remission (NCR) compared to those in complete remission (CR). ROC analysis further highlighted the predictive capability of serum SDF-1 alpha for chemotherapy responsiveness. Independent predictors of treatment failure included age, FAB classification, ECOG status, and serum SDF-1 alpha levels. Following chemotherapy, serum SDF-1 alpha levels decreased in patients in CR but remained unchanged in those in NCR. Higher baseline levels of SDF-1 alpha were associated with shorter overall survival. Conclusions Elevated serum SDF-1 alpha levels in elderly AML patients are associated with poor chemotherapy response and shorter survival. Baseline serum SDF-1 alpha levels could serve as a prognostic marker for CAG-based treatment outcomes.