Background: High altitude is known to have a significant impact on human physiology and health, therefore, understanding its relationship with quality of life is an important research area. This study compared the quality of life (QOL) in older adults living in high and low altitude areas, and examined the independent correlates of QOL in those living in a high altitude area. Methods: Older adults living in three public nursing homes in Xining (high altitude area) and one public nursing home in Guangzhou (low altitude area) were recruited. The WHOQOL-BREF was used to measure the QOL. Results: 644 older adults (male: 39.1%) were included, with 207 living in high altitude and 437 living in low altitude areas. After controlling for the covariates, older adults living in the high altitude area had higher QOL in terms of physical (P = 0.035) and social domains (P = 0.002), but had lower QOL in psychological (P = 0.009) domain compared to their counterparts living in the low altitude area. For older adults living in the high altitude area, smoking status was associated with higher social QOL (P = 0.021), good financial status was associated with higher physical QOL (P = 0.035), and fair or good health status was associated with higher physical (p < 0.001) and psychological QOL (P = 0.046), while more severe depressive symptoms were associated with lower QOL. Conclusion: Appropriate interventions and support to improve depressive symptoms and both financial and health status should be developed for older adults living in high altitude areas to improve their QOL.