Climate change and shrinking of the Aral Sea have significantly affected the region’s temperature variations. Observed interannual changes in Uzbekistan’s air temperature compared to the duration of synoptic weather types (SWT) in Middle Asia were analyzed. Nonparametric Mann–Kendall statistical test and climate trends coefficients were used to identify trend characteristics of observed temperature from 1961–2016 to the baseline period of 1961–1990. The results showed increasing temperature trends average to 1 °C in warm and cold half years over Uzbekistan. The 1991–2016 decadal temperature trend ranged from 0.25 °C/decade in the northwest to 0.52 °C/decade in the center, especially pronounced in the oasis and Aral Sea zones. There were also significant changes in the structure of regional SWT. The main difference in the structure of SWT in Middle Asia relative to the baseline period was expressed in a decrease of cold mass invasion duration from 113.4 to 76.1 days and an increase in low-gradient baric field duration from 65.8 to 134.6 days. The process of anthropogenic warming, which began in Uzbekistan in the 1960s of the twentieth century, has accelerated from the mid-1970s with a higher mean annual air temperature than the baseline period’s climate normals (1961–1990) and is associated with changes in the regional SWT over Middle Asia.