[Objective] The spatial-temporal changes and the driving mechanisms of landscape ecological security (LES) in the lower reaches of the Lancang River were analyzed to provide scientific basis for the coordinate and sustainable development of human and nature in the basin and the downstream countries. [Methods] By using the remote sensing images of 2005, 2010, 2015, and 2018, this study assessed the LES of the lower reaches of Lancang River by landscape index and GIS technology. The bivariate spatial autocorrelation was used to simulate the driving mechanism of regional factors (including cities, roads, rivers, elevation, slope, temperature and precipitation) on spatial-temporal changes of LES. [Results] ① From 2005 to 2018, the LES increased firstly and then decreased in the lower reaches of Lancang River. The LES in the northern and mid-west regions was relatively poor, which in the eastern, southern, and southeastern regions was better but also showed a tendency of deterioration. ② The LES of various landscape types was as: waters > forestland > grassland > cultivated land > construction land > bare land. Among them, the LES of forestland and grassland fluctuated, the LES of the cultivated land and waters increased, while the LES of construction land and bare land decreased. ③ Social and meteorological factors, such as distance form cities, distance from roads, temperature and precipitation, showed the strongest influence on spatial-temporal changes of the LES. And the distance from rivers also explained the spatial-temporal change of the LES at certain extent. The topographical factors such as elevation and slope showed no influence on spatial-temporal changes of LES in the lower reaches of Lancang River. [Conclusion] In the future, the eco-environmental load caused by human activities should be reduced as much as possible, and the positive effects of meteorological factors on ecological security should be brought into full play, to promote the coordinate and sustainable development of human and nature in the lower reaches of Lancang River.