The Ugan-Kuqa river oasis, a typical desert oasis area in the northwest arid area, is a vital guarantee for sustainable development of the oasis. In this study, three phases of Landsat TM images obtained in 1997, 2006, and 2016 were used as the main data sources to construct an ecological security evaluation model for the Ugan-Kuqa river oasis landscape, and spatial and temporal differentiation of the landscape ecological security in the last 20 years was analyzed. The minimum resistance model was used, with water and forest-grassland as the ecological sources of the oasis. The resistance surface was generated with resistance factors, such as levels of ecological safety, altitude, and slope; the ecological function area was divided; and the ecological corridor and node were identified, which promised that the landscape pattern was optimized from the point, line, and surface. The results were as follows: (1) From 1997 to 2016, the ecological security area of the Ugan-Kuqa river oasis fluctuated as the relative security area increased and the area of critical security, sensitivity, and risk area decreased. The ecological security degree of the Ugan-Kuqa river oasis tended to expand outwards from high to low. (2) Moran's I values for landscape ecological security in the study area were 0.6479, 0.7049, and 0.6587. The spatial clustering of landscape ecological security values first increased and then decreased. Local spatial auto-correlations were mainly high-high and low-low aggregations, presenting the characteristics of "homogeneous aggregation and heterogeneous separation". (3) The ecological source area of the Ugan-Kuqa river oasis accounted for 12.76% of the total area, and the ecological corridor network of the oasis ran through the whole research area. The key corridor connected most of the ecological sources of the oasis, whereas the auxiliary corridors were linked to the rest ecological sources. A total of 36 recognized ecological nodes, which were mainly distributed in the weak link of the oasis ecological corridors. The ecological safety network combined the ecological buffer zone, the ecological connectivity zone, the ecological transition zone, the ecological margin zone, the five functional zones, the ecological source zone, the ecological corridor and the ecological node landscape components. According to the ecological safety network, the optimization proposal was proposed to provide a scientific basis for maintaining and further improving the ecological environment of the oasis.