Over the last decade, lithium-sulfur (Li-S) batteries have been thought of as promising alternatives for the new generation of the battery systems. Although the Li-S batteries possess high theoretical energy density (2600 Wh kg-1) and capacity (1675 mAh g-1), the problems of poor electron and ion conduction, volumetric expansion and sulfur immobilization greatly impede the wide applicability of Li-S batteries. Herein, a defect-rich multi-shelled Co3O4 microsphere structure doped with Fe was synthesized via a one-step hydrothermal method and a subsequent thermal treatment. The unique multi-shelled structure provides multiple spatial confinements for lithium polysulfides (LiPs) trapping and buffers the volume variation during cycling. Moreover, the rich oxygen-defect designed by controllable Fe doping can provide numerous catalytic sites for polysulfide redox reactions. Attributed to the synergistic effect of structural design and oxygen-defect fabrication, the sulfur composite electrode delivers a notable cycle performance, presenting a much lower capacity fading of 0.017% per cycle over 1000 cycles at 1 C and excellent rate capability of 571.3 mAh g-1 at 5 C. This work proposes a potential approach for designing transition-metal-oxide (TMO) based multi-shelled hollow structure combined with oxygen-defect, which also offers a new perspective on high-performance Li-S batteries.