Background Circ_0072995 is a novel identified circRNA and has been identified to involve in the metastasis of breast cancer. However, the detailed function and mechanism of circ_0072995 in the biological property of breast cancer cell remain vague. Methods The expression of circ_0072995, microRNA (miR)-149-5p and serine hydroxymethyltransferase 2 (SHMT2) mRNA was detected using quantitative real-time polymerase chain reaction. Western blot was used to detect levels of SHMT2, hexokinase-2 (HK-2), lactate dehydrogenase a chain (LDHA), glucose transporter 1 (GLUT1) and phosphoinositide 3-kinase (PI3K)/p-protein kinase B (AKT) pathway/mammalian target of rapamycin (mTOR) pathway-related protein. Cell proliferation, apoptosis, migration, and invasion were analyzed using cell counting kit-8 assay, flow cytometry, caspase-3 activity analysis, cell adhesion assay and transwell assay, respectively. Glucose metabolism was calculated by measuring glucose uptake, lactate production, and adenosine triphosphate (ATP) levels. The interaction between miR-149-5p and circ_0072995 or SHMT2 was confirmed by dual-luciferase reporter assay. In vivo tumorigenesis was performed using the murine xenograft model. Results Circ_0072995 and SHMT2 were up-regulated in breast cancer tissues and cell lines, and knockdown of circ_0072995 or SHMT2 suppressed cell malignant properties and anaerobic glycolysis; importantly, SHMT2 overexpression attenuated the anticancer action of si-Circ_0072995 in breast cancer. Besides, we also found miR-149-5p directly bound to circ_0072995 or SHMT2 in breast cancer cells, and circ_0072995 promoted the expression of SHMT2 by competitively binding to miR-149-5p. Moreover, circ_0072995 activated PI3K/AKT/mTOR pathway via elevating SHMT2 through miR-149-5p in vitro and in vivo. Additionally, xenograft tumors analysis showed circ_0072995 silence suppressed tumor growth via regulating SHMT2 and miR-149-5p. Conclusion This study demonstrated that circ_0072995 promoted cell malignant phenotypes and anaerobic glycolysis in breast cancer via up-regulating SHMT2 through sponging miR-149-5p, and activated PI3K/AKT/mTOR pathway via miR-149-5p/ SHMT2 axis, indicating a promising molecular target for breast cancer treatment.