Grain production is vital to the national economy and people’s livelihood, and improving grain production efficiency is of great significance to the sustainable development of China’s economy and society. From the perspective of financial support, using the DEA global Malmquist productivity index model and based on the data of 13 main grain producing areas in China from 2001 to 2017, this paper discusses the evolution characteristics and regional distribution differences of the total factor productivity index of grain production in China’s main grain producing areas. The results show that from 2001 to 2017, the total factor productivity index of grain production in China’s main grain producing areas showed an overall fluctuation trend of gradual decline, with an average annual decline of 7.3%. From the perspective of spatial analysis, the grain production efficiency in China’s main grain producing areas is characterized by uneven spatial development, which is generally manifested as the decreasing trend from the central region to the eastern and western regions. Meanwhile, it can be seen from the decomposition index that the change of total factor productivity of grain production in China’s main grain producing areas mainly depends on the change of technical efficiency.