The northern snakehead (Channa argus) is extensively distributed throughout rivers and lakes of China. With overexploitation and water eco-environment deterioration, the resources of C. argus are severely affected. To examine genetic structure and the demographic history of the northern snakehead, we collected 212 specimens from 8 locations for generating mitochondrial DNA complete control region sequences. Result showed that the length of control region is about 907 bp. The genetic diversity in southern China is higher than that in the north with boundary line 34°N. The factors that warm and wet climate in the south China and dry and cold climate in the north China, and that the rapid uplift of Qinling Mountain aggravated differentiation of the east Asian monsoon, may have an important influence on genetic diversity. The phylogenetic tree showed a shallow genealogy and high genetic differentiation and significant level of genetic structure which behaved in different drainages. This indicated that geographical barriers led to recent genetic differentiation. The demographic history of 7 populations of China displayed that the northern snakehead experienced population rapid growth in the interglacial period of the middle Quaternary. Then, the demography declined during the last glacial period. With climatic warming in the Holocene, a slight population growth happened. The Dongting Lake population also experienced a population expansion in the interglacial period of the middle Quaternary. The glacial-interglacial cycles in the Quaternary, especially from the middle Quaternary, caused pronounced climatic fluctuations and had an important influence on the northern snakehead populations. Information on genetic diversity and genetic structure will have implications for the management of fisheries and conservation efforts.