The present study aimed to explore the cortical activity underlying mental rotation in high-altitude immigrants via the event-related desynchronization (ERD), the electroencephalogram time–frequency analysis, and source localization based on electroencephalographic data. When compared with the low-altitude individuals, the reaction time of mental rotation tasks was significantly slower in immigrants who had lived in high-altitude areas for 3 years. The time–frequency analysis showed that the alpha ERD and the beta ERD within the time window (400–700 ms) were decreased during the mental rotation tasks in these immigrants. The decreased ERD was observed at the parietal–occipital regions within the alpha band and at the central–parietal regions within the beta band. The decreased ERD might embody the sensorimotor-related cortical activity from hypoxia, which might be involved in cognitive control function in high-altitude immigrants, which provided insights into the neural mechanism of spatial cognition change on aspect of embodied cognition due to high-altitude exposure.