Assembling transition-metal oxides (TMOs) and MXene with strong interfacial interactions is an effective method to overcome the drawbacks of TMOs as anodes for lithium-ion batteries (LIBs) such as large volume expansion and low conductivity. Herein, a CuO nanorod/MXene heterojunction (denoted as CuO/MXene) with a synergistic effect was constructed with a "sheet-rod-pore" hierarchical nanostructure by electrostatic self-assembly. Specifically, encapsulated CuO nanorods exert superiority in the high reversible capacity and increase the interlayer distance of the MXene matrix to explore more storage spaces. MXene could significantly boost the conductivity, accommodate volume variation, and inhibit structure collapse as a buffer network. Density functional theory (DFT) calculations confirm the strong electron transport and lithium affinity at the CuO/MXene heterointerface, elucidating the reasons for the enhanced lithium storage capacity (436.4 mAh g −1 at 500 mA g −1 ), ion diffusion kinetics, and structural stability after cycling than pure CuO and MXene. When paired with the LiCoO 2 cathode, the full cell delivers good cycling stability after 140 cycles, indicating the practical applicability of CuO/MXene. This work not only validates the robust interfacial interaction of TMO/MXene heterojunction but also explores an effective strategy to prepare promising anode materials for the next-generation LIBs.