CoFe2O4 spheres were synthesized using a microwave-hydrothermal reaction and characterized by X-ray diffraction, electron microscopy, and electrochemical analysis. This simple synthesis method led to a uniform dispersion of nanosized building blocks in the spheres, which exhibit significantly improved cycling performance and rate capability in lithium cells. The excellent electrochemical performances of CoFe2O4 sphere are attributed to an increased lithium wetting property at the electrode–electrolyte interface, facile lithium-ion diffusion, and better alleviation of the structure pulverization during charge–discharge process.