Recently, Ti-based MXenes were expected to compete with graphene and other carbonaceous materials towards Li-ion batteries (LIBs) due to their two-dimensional (2D) open structure, cost efficiency, superior conductivity and low Li+ diffusion barrier. However, the relatively moderate capacity and aggregation tendency hamper their practical applications in next-generation LIBs. Herein, we explore for the first time a scalable bottom-up approach to fabricate a series of Co3O4@single-layer Ti3C2Tx (s-Ti3C2Tx) hybrids, where numerous homogeneous Co3O4 nanocrystallites (NCs), serving both as a spacer and electroactive phase, are anchored uniformly on the surface of s-Ti3C2Tx nanosheets (NSs) through the Co-O-Ti interfacial bonds. Furthermore, detailed experimental analyses clearly shed light upon the formation mechanism of the hybrid Co3O4@s-Ti3C2Tx NSs. Thanks to the structural and compositional merits, the 2D Co3O4@s-Ti3C2Tx NSs even exhibit a remarkable high-rate capacity of ∼223 mA h g-1 at an ultra-high current density of 10 A g-1, and a long-span cycle life with a high reversible capacity of 550 mA h g-1 at 1 A g-1 after 700 consecutive cycles. Corresponding density functional theory calculation further confirms that the Co-O-Ti interfacial function leads to an even higher pseudocapacitive contribution and faster lithium storage behavior due to the enhanced interfacial electron transfer.