Abstract: Excessive application of chemical fertilizer has caused the ever-increasing agricultural non-point source pollution in recent years. Great efforts were made to control agricultural pollution, and thereby explore the changing characteristics and driving factors for the application intensity of chemical fertilizer. The amount of chemical fertilizer was widely expected to be reduced, further to enhance the efficiency of chemical fertilizer application and green development of agriculture. Taking the Enshi Prefecture of Hubei Province in central China as an empirical case, this study aims to determine the spatio-temporal variation characteristics and the driving force of chemical fertilizer application. Logarithmic Mean Divisia Index (EMDI) exponential decomposition and panel regression models were established to comprehensively consider the efficiency of fertilizer application, regional fertilization structure, agricultural technology development, multiple planting index, and agricultural acreage. The results showed as follows: 1) The fertilizer application in the study area increased firstly, then steadily, and finally decreased over the last ten years. The ratio of nitrogen, phosphorus and potassium increased from 1:0.30:0.15 in 2007 to 1:0.39:0.26 in 2018, gradually approaching the level of developed countries in the world. There were one low-intensity zone, two medium-intensity zones, four high-intensity zones, and one ultra-high intensity zone by 2018 for chemical fertilizer application in the study area. 2) Chemical fertilizer application in the study area decreased by 7 008.32 t in 2016, 3 341.65 t in 2017, and 15 059.81 t in 2018, compared with the previous year. The efficiency increase of fertilizer application reduced the amount of fertilizer application by 11 159.44, 14 051.95 and 8 644.21 t in the last three years. The multiple cropping index reduced the amount of fertilizer application by 5 229.76 t in 2017, and 30 889.98 t in 2018. There was no significant effect value in 2016. The development of agricultural technology increased the amount of fertilizer application by 4 089.71, 11 136.97 and 12 215.74 t in 2016, 2017 and 2018. But there was no significant driving effect of regional structure. 3) There were positive effects of three factors to reduce the application amount of chemical fertilizer, including the economic development, adjustment of agricultural structure, and expansion of financial scale. But the population increase presented negative effects in this case. It is suggested to change the direction of agricultural technology development, from merely increasing production to multi production with high efficiency. The effective arable land area should also be reasonably adjusted, in order to further improve the efficiency of chemical fertilizer application. A model of ecological security and green development should be fostered to promote the reduction of chemical fertilizers and the increase of efficiency in modern agriculture.