The main pressing problems should be solved for heterogeneous catalysts in activation of peroxymonosulfate (PMS) are sluggish mass transfer kinetics and low intrinsic activity. Here, oxygen vacancies (Vo)-rich of Co3O4 nanosheets were anchored on the superficies of spirulina-based reduced graphene oxide-konjac glucomannan (KGM) aerogel (R-Co3O4-x/SRGA). The porous structure and superhydrophilicity conferred by KGM maximized the diffusion and transport of reactant. More interestingly, R-Co3O4-x/SRGA came true self-suspension rather than conventional self-floating without the aid of external force, maximizing space utilization and facilitating catalysts recovery. Anchored R-Co3O4-x nanosheets acted as “engines” to drive the reaction. Density functional theory (DFT) manifested Vo was capable of breaking the symmetry of the electronic structure of Co3O4. The formation of asymmetric active sites (Vo) was revealed to modulate the d-band center, enhanced affinity for PMS, and promoted evolution of high-valent cobalt-oxo (Co(IV)=O) species. R-Co3O4-x/SRGA achieved complete removal of sulfamethoxazole (SMX) within 12 min. Furthermore, R-Co3O4-x/SRGA demonstrated exceptional stability in the presence of various environmental interference factors and continuous flow device. This insightful work cleverly integrates the macroscopic design of structure, and the microscopic regulation of active sites is expected to open up new opportunities for the development of water treatment.