Here, we report that spherical C60 derivatives with well-defined molecular structures hold great promise to be advanced anode materials for lithium-ion batteries (LIBs). We studied four C60 molecules with various functional groups, including pristine, carboxyl, ester, and piperazine C60. The comparison of these C60s elucidated a strong correlation between functional group, overall packing (crystallinity), and the anode performance in LIBs. Specifically, carboxyl C60 and neutral ester C60 showed higher charge capacities than pristine C60, whereas positively-charged piperazine C60 exhibited lower capacity. The highest charge capacity was achieved on the carboxyl C60 (861mAhg−1 at 100th cycle), which is five times higher than that of pristine C60 (170mAhg−1), more than double the theoretical capacity of commercial graphite (372mAhg−1), and even higher than the theoretical capacity of graphene (744mAhg−1). Carboxyl C60 also showed a high capacity at a fast discharge-charge rate (370mAhg−1 at 5C). The exceptional performance of carboxyl C60 can be attributed to multiple key factors. They include the complex formation between lithium ions and oxygen atoms on the carboxyl group, the improved lithium-binding capability of C60 cage due to electron donating from carboxylate groups, the electrostatic attraction between carboxylate groups and lithium ions, and the large lattice void space and high specific area due to carboxyl functionalization. This study indicates that, while maintaining the basic C60 electronic and geometric properties, functionalization with desired groups can achieve remarkably enhanced capacity and rate performance for lithium storage.