Sustainable Livelihood Security (SLS) remains a rarely considered yet important issue for rural sustainability and natural resource management. Particularly in China, rural SLS research in a typical area is urgently needed, but insufficient under the background of National Rural Revitalization and Ten-year Fishing Ban of Yangtze River. Focusing on the policy-targeted inland lake area, we proposed a Livelihood Security Analysis (LSA) framework by establishing an adaptive indicator system and integrating multiple econometrical and geographical methods. This study aims to evaluate the SLS in Poyang Lake Eco-economic Zone comprehensively from the three aspects of ecology, economy and society, analyze their spatial patterns, identify the main constraints, and finally give specific suggestions for improving rural sustainability management. The results showed that rural SLS in the inland great lake area tended to be vulnerable mainly due to the lagging economic efficiency and unbalanced social equality, and mediated by regional ecological characteristics. The overall SLS and Ecological Security Index (ESI) were higher in the north and lower in the south, while Economic Efficiency Index (EEI) and Social Equality Index (SEI) were at the middle level and circularly distributed around Nanchang City. The dominating factors which have greatly shaped the spatial pattern of SLS include rural per capita electricity consumption, fishery breeding area, population dependency ratio, urbanization rate, and fishery population. The obstacle degree is ranked as economic system > social system > ecological system. An outdated economy and incomplete social services are the main constraints, characterized by weak electricity consumption, limited beds in hospitals, low urbanization rate, deficient agricultural machinery power, and a small agricultural output value. Therefore, one urgent need is to activate the rural economy by reinforcing rural electric power facilities and promoting agricultural mechanization. In addition, transforming the peasants/fishermen to the non-agricultural sector should be accelerated, which will help to reduce ecological pressure, boost urban-rural integration and narrow the income gap.