Poor water stability and difficult separation severely limited the application of Co-based catalysts in persulfate activation. Herein, for the first time, the calcium alginate-immobilized Co-g–C3N4–2 composite microspheres were prepared by a feasible method. Notably, embedding Co ion into g-C3N4 can improve its specific surface area and electrochemical activities. More significantly, as-prepared Co-g–C3N4–2 microsphere presented excellent catalytic performance in PMS activation for the degradation of TC. For the activation mechanisms of PMS over Co-g–C3N4–2 microspheres, the calcium alginate microspheres could mediate the direct electron transfer between TC and PMS, while both radical and nonradical pathways were involved in the activation of PMS over Co-g–C3N4–2. Meanwhile, SO4•−, OH•, O2•− and 1O2 were major reactive oxygen species formed in the Co-g–C3N4–2 microsphere/PMS system. Proposed Co-g–C3N4–2 microsphere/PMS system still exhibited great degradation ability towards TC over a wide pH range, and co-existing anions had weak influence on TC degradation over Co-g–C3N4–2 microsphere/PMS system. Moreover, the construction of Co-g–C3N4–2 microspheres not only avoided the release of metal ion from catalyst, but also provided convenience for the recovery of catalyst. In short, current work shared some novel insights into the application of heterogeneous catalysis in persulfate activation for wastewater treatment.