Given the restrictions on special geographic locations in development processes, the measurement and analysis of the ecological quality of the Hami Oasis are of great significance for the protection of this fragile oasis. In this study, the ecological quality of the Hami Oasis was monitored by constructing a remote sensing ecological index (RSEI) for arid areas. Using the standard deviation ellipse and moving window method, the ecological status and space–time changes were explored for both their external and internal factors in the Hami Oasis. Finally, a geo-detector was employed to determine the driving factors of the ecological quality of the Hami Oasis. The results revealed that: (1) In the remote sensing ecological index constructed in the Hami Oasis, the main influencing factors were dryness and wetness. The average value of the ecological quality of the oasis was less than 0.5, and the ecological quality level was relatively poor. Among the five grades of ecological quality in the Hami Oasis, the poor grade and the good grade showed the largest changes, decreasing by 200 and increasing by 300, respectively, which were mainly concentrated in the periphery of the oasis. (2) The improved ecological quality of the Hami Oasis was mainly manifested in the expansion of the artificial oasis, while the deteriorated area was manifested as an increase in the built-up area. Moreover, the ecological quality of the Hami Oasis presented a ringlike nesting distribution pattern from the internal built-up area to the artificial oasis periphery. (3) The external expansion direction of the ecological quality of the Hami Oasis featured southeast–northwest expansion, which was consistent with the direction of the rivers and traffic roads. The transformation between different ecological qualities in the oasis and the expansion of the built-up area were the reasons for the fragmentation of the Hami Oasis’ landscape. (4) Compared to a single factor, the dual-factor for the ecological quality of the Hami Oasis had stronger explanatory power. Moreover, changes in land use types caused changes in the ecological quality of the Hami Oasis. During the study period, we found that human activities had a more significant impact than natural factors on the development of the Hami Oasis. (5) The Moran’s I Index increased from 0.835268 in 2000 to 0.923976 in 2018, and the p values in the study area all reached a 0.05 significant level. At the same time, the areas with p values above the 0.01 and 0.001 significant levels have also increased significantly in the past 18 years.