Abstract: Pesticide overapplication has posed quite a serious threat to the ecological environment of agricultural systems in recent years. At the same time, grain production is highly concerned with ensuring national food security in China. Therefore, it is of great significance to improve the use efficiency of pesticides, according to local conditions. This study aims to clarify the spatiotemporal evolution and influence factors of excessive pesticides in the major staple grain production of China from 2000 to 2022. The provincial panel data was then selected for the pesticide application in the three major grains of rice, wheat, and corn. The degree of pesticide overapplication was also quantitatively measured, according to the damage control function model, GIS spatial analysis, and the panel economic model. The results show that: (1) There was an outstandingly fluctuant increase in the actual, optimal, and overapplication of pesticides in the production of the three major grains from 2000 to 2022. The average value was ranked in the descending order of the rice > wheat > corn. Furthermore, there was a relatively small variation in the regional pattern of the three major grains. Similar levels of pesticide overapplication were observed between the eastern and central regions, as well as the western and northeastern ones. Nevertheless, the overapplication levels in the former two regions were significantly higher than those in the latter two. (2) In the provincial spatiotemporal evolution, the overall level of pesticide overapplication in the rice production areas shifted from the slight to the moderate excess spectrum from 2000 to 2022. While the spectrum of no excess was shifted to the moderate one in the wheat and maize production areas. Moreover, the moderate and severe excess areas in rice production were highly concentrated in the eastern and central regions. (3) Six influencing factors were determined with the varying significant inhibiting effects on the pesticide overapplication, including urbanization rate, average grain production scale per household, education level of farmers, fiscal expenditure on agriculture, cultivated land transfer areas, and the policy of zero growth in pesticide application. Conversely, the five factors shared varying significant promoting effects, including the temperature, natural disasters, GDP per capita, grain prices, and per capita disposable income of rural residents. The space size was clarified to reduce the application of pesticides for its use efficiency in the three major grains production. The finding can also provide the decision-making on the ecological environment in different regions of China.