Background. Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. Circular RNAs (circRNAs) play crucial roles in AML progression. This study aimed to explore the function and potential mechanism of circRNA Scm like with four mbt domains 2 (circ-SFMBT2; hsa_circ_0017639) in AML. Methods. The levels of circ-SFMBT2, microRNA-582-3p (miR-582-3p) and zinc finger and BTB domain containing 20 (ZBTB20) were measured by quantitative real-time PCR and Western blot. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry and transwell assays were used to evaluate cell proliferation, apoptosis, migration and invasion. Glycolysis was assessed by detecting glucose consumption, lactate production and ATP/ADP ratios. The related protein expression was examined by Western blot. The binding relationship between miR-582-3p and circSFMBT2/ZBTB20 was verified by dual-luciferase reporter assay. Results. Circ-SFMBT2 and ZBTB20 levels were elevated, while miR-582-3p level was reduced in AML patients and cells. Depletion of circ-SFMBT2/ZBTB20 impeded proliferation, migration, invasion and glycolysis and induced apoptosis in AML cells. Moreover, circ-SFMBT2 facilitated AML progression by sponging miR-582-3p, and miR-582-3p targeted ZBTB20 to hinder AML development. Conclusion. Knockdown of circ-SFMBT2 suppressed AML progression by regulating the miR-582-3p/ZBTB20 axis, which might provide a potential therapeutic strategy for AML.