The Sahara Desert is the largest source of dust on Earth, and has a significant impact on global atmospheric changes. Wind is the main dynamic factor controlling the transport and intensity of dust in the Sahara Desert. This study comprehensively analyzed the spatial and temporal variation in the wind regime of the Sahara Desert from 1980 to 2019 using data from 17 meteorological stations to improve awareness of global atmospheric changes and the intensity of regional aeolian activities. All wind speed parameters decreased from northwest to southeast. While there were significant differences in the trends of temporal variation in wind speed among the different regions, there was an overall decreasing trend across the Sahara Desert, with an average wind speed of 0.09 m s−1 10 a−1. This decrease was closely related to wind frequency. The easterly, westerly, and northerly winds dominated, with more complex wind direction in the northern region. Seasonal differences in wind direction were observed in all regions. The wind direction frequency of wind speeds >6 m s−1 exceeded those with wind speeds <6 m s−1 in the western and northern regions, whereas other regions showed an opposite pattern. The highest drift potential (DP) and resultant drift potential (RDP) were found in the western and northern regions, and during spring and winter. There was a trend of decreasing annual variation in DP and RDP in all regions. The directional variability (RDP/DP) indicated mostly intermediate and high variability in wind direction. Resultant drift direction (RDD) indicated that a mainly southwest wind direction. No apparent trends in temporal variation in RDD and RDP/DP were observed. Total DP was strongly influenced by DP and the magnitude and frequency of strong winds in the prevailing wind direction. No strong correlation between wind regimes and dune types was observed in this desert, indicating the complexity of factors affecting dune morphology.