Under the background of global warming, China has experienced frequent natural disasters that have seriously affected grain production in recent decades. Based on historical documents from 1978–2014, we explored the spatio-temporal variation of five major kinds of natural disasters and grain losses in China using statistical techniques: the Mann-Kendall (MK) test, social network analysis (SNA), and geographic information system (GIS) tools. The disaster intensity index (Q) clearly showed the variation of natural disasters; all of China experienced a significant increasing trend at an annual scale, reaching its peak (27.77%) in 2000. The step change points in floods, droughts, hail, and low-temperature events began to occur in 1983, 1988, 1988, 1992, respectively, while no obvious trend was detected for typhoon activity from 2001 to 2014. Drought and flood were the most serious types of disaster over the last four decades, accounting for more than 50% of total grain losses. Eight major provinces were identified with severe grain losses: Heilongjiang, Shandong, Henan, Hebei, Anhui, Sichuan, Jiangsu, Hunan, and Hubei. Five studied natural disaster types were identified throughout the seven physical geographical regions. Spatial distribution for the different disaster types showed significant geographical distribution characteristics. Natural disasters gradually became more diverse from north to south. Droughts, hail, and low-temperature disasters were randomly distributed throughout China; flood and typhoon disasters exhibited significant spatial auto-correlation and clustering patterns. Finally, in accordance with the intensity of natural disaster, the annual grain losses at the provincial scale initially increased (ranging from 0.14 million to 3.26 million tonnes in 1978–2000), and then decreased after 2000 (ranging from 3.26 million to 1.58 million tonnes in 2000–2014). The center of gravity of grain losses gradually moved northward. These results emphasize that developing different strategies for disaster prevention and mitigation programs in the major grain producing areas (e.g., Heilongjiang, Shandong, and Henan) are critical and important to China’s food security.