To combat groundwater pollution, in situ chemical oxidation (ISCO) has been extensively adopted to degrade groundwater pollutants. A critical factor associated with the success of ISCO is the stability (or persistence) of the chemical oxidant. A higher oxidant stability can result in a higher integrity and a sustained oxidation capacity for the oxidants. Both potassium permanganate (KMnO) and persulfate (PS) are two most commonly employed chemical oxidants for ISCO operations. Although a number of experimental studies have been conducted to evaluate the persistence of these two oxidants, systematic investigations of the persistence of KMnO and PS and especially the impact of different subsurface materials on oxidant stability are still limited. To fill these knowledge gaps, the stability of both KMnO and PS oxidants has been systemically evaluated in this study. For each type of oxidant, the impact of solution pH and the presence of matrix anions on oxidant stability were evaluated. Furthermore, the persistence of these oxidants was examined in the presence of a number of soils and subsurface minerals with the natural oxidant demand value of each subsurface material being determined. It is found that KMnO can directly react with the reducing constituents in the soils via chemical oxidation where PS requires to be activated first in order to produce sulfate radical to react with reducing species. This study provides the essential information of the stability of KMnO and PS under different physiochemical conditions and in the presence of different subsurface materials for groundwater ISCO treatment. The conclusions from this study can substantially facilitate the ISCO operations by use of KMnO and PS in a more efficient and cost-effective manner.