Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell malignancy characterized by the BCR-ABL1 fusion oncogene. Although tyrosine kinase inhibitors (TKIs) have improved survival, suboptimal treatment response and disease progression remain significant challenges, especially in resource-limited settings such as Nigeria and sub-Saharan Africa. MicroRNA-451 (miR-451) has emerged as a potential biomarker due to its regulatory role in cell proliferation, apoptosis, and drug sensitivity. To systematically evaluate miR-451 gene expression in CML patients and assess its clinical relevance, including diagnostic, prognostic, and therapeutic potential in African populations. A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. PubMed, Scopus, Web of Science, and EMBASE were searched for studies reporting miR-451 expression in CML up to June 2025. Data were pooled using standardized mean differences (SMDs) with 95% confidence intervals (CIs) under a random-effects model. Subgroup analyses were conducted by disease phase, treatment status, detection method, and geographic region. Study quality was assessed using a modified Newcastle– Ottawa Scale. Publication bias was evaluated with funnel plots and Egger’s regression test. Twelve studies including 654 CML patients and 412 healthy controls were analyzed. miR-451 was significantly downregulated in CML patients compared with controls (SMD = −1.23, 95% CI −1.65 to −0.82, p <0.001), with greater reductions in advanced disease phases and treatment-naïve patients. Findings from Nigeria and other African studies were consistent with global trends. Sensitivity analyses confirmed result robustness, and no significant publication bias was detected. miR-451 is consistently downregulated in CML and is associated with disease progression and treatment response. It shows promise as a diagnostic, prognostic, and therapeutic biomarker, particularly in resource-limited settings. Further validation in African cohorts is recommended.