© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Lithium-ion batteries (LIBs) have been widely applied and studied as an effective energy supplement for a variety of electronic devices. Titanium dioxide (TiO2), with a high theoretical capacity (335 mAh g−1) and low volume expansion ratio upon lithiation, has been considered as one of the most promising anode materials for LIBs. However, the application of TiO2 is hindered by its low electrical conductivity and slow ionic diffusion rate. Herein, a 2D ultrathin mesoporous TiO2/reduced graphene (rGO) heterostructure is fabricated via a layer-by-layer assembly process. The synergistic effect of ultrathin mesoporous TiO2 and the rGO nanosheets significantly enhances the ionic diffusion and electron conductivity of the composite. The introduced 2D mesoporous heterostructure delivers a significantly improved capacity of 350 mAh g−1 at a current density of 200 mA g−1 and excellent cycling stability, with a capacity of 245 mAh g−1 maintained over 1000 cycles at a high current density of 1 A g−1. The in situ transmission electron microscopy analysis indicates that the volume of the as-prepared 2D heterostructures changes slightly upon the insertion and extraction of Li+, thus contributing to the enhanced long-cycle performance.