Cultivated land is the most precious treasure in land resources. It is the foundation of human's survival and development, and the guarantee of food and ecological security in regional level. The protection of agricultural land is now the core issue in the strategy of sustainable development among countries, and regarded as the national policy of China. Nevertheless, the national policy and its strategies did not effectively prevent the agricultural land from huge loss in recent years, and the phenomenon is significantly worse in south Jiangsu Province which experiences the most rapid industrialization across China. As time goes by with the acceleration of urbanization and industrialization, considerable amount of cultivated land resource has been consumed with the deteriorated ecological environment and the fragmented landscape. Thus summarizing the spatio-temporal change characteristics and identifying the main direction and impact factors of cultivated land loss in longitudinal study of the land use change in south Jiangsu Province would have crucial meaning for enhancing the sustainable development of regional Socio-economy and eco-environment. Based on three periods land-use historical data extracted from high-resolution remote sensing images of Xinzhuang Town in south Jiangsu Province, integrated with GIS spatial analysis and statistical method, we selected landscape dynamic degree and shrinking intensity index to analyze the decreasing speed and intensity of paddy field in each village, utilized transfer matrix and GIS map overlay to analyze the spatio-temporal characteristics of paddy landscape change, and took advantage of redundancy analysis to directly clarify the correlation between environmental variables (Socio-economic and neighborhood factors) and the major paddy-related land use transformation. The results showed that 30.5% of the total paddy field lost during 1991-2009 in Xinzhuang Town, with an accelerated decreasing trend; the losing size, speed and intensity of paddy field of different village varied considerably. During the period of 1991-2001, the paddy fields were mainly invaded by fishpond and residential land, and the invasion usually occurred along with rivers and main roads. During the period of 2001-2009, the paddy fields were mainly occupied by industrial land, fishpond and residential land, and the occupation of industrial and residential land usually occurred along the main roads, and the occupation of fishpond usually occurred near the rivers. In the periods of 1991-2001 and 2001-2009, the influence factors are applied separately to explain the main spatial variation of paddy field landscape change as 50.31% and 69.27%. It also found that each factor has significant difference for explaining the spatial variation of the paddy field change in different periods. In the period of 1991-2001, the density of population, the per capita income of farmers, and the distance to roads and rivers are supposed to be extremely significant factors which could affect the change process (from paddy field to residential land). Further, the distance to residential area, local councils and rivers are also revealed as the main impact factors which could affect the change process (from paddy fields to industrial land); In period of 2001-2009, the major impact factors become the distance to rivers and roads that could affect the change (from paddy fields to industrial lands), and the density of population, the per capita GDP, per capita income of farmers, and the distance to local councils and residential area also significantly affect the change process of paddy fields (toward residential land). On the other hand, the change process from paddy fields to fishpond are highly relevant to the per capita agricultural output value, the unit area output of grain, and the distance to roads and rivers. In all, it is found that most of the losing paddy area was occupied by industrial land, fishpond and residential land, and this phenomenon was concentrated around the main roads and rivers. A big proportion of the variance in paddy-related land use transformation was explained by Socio-economic factors and neighborhood factors, and the role of each factor played in different periods varied greatly.