The widely distributed glaciers over the Qinghai-Tibet Plateau (QTP) represent important freshwater reserves and the meltwater feeds many major rivers of Asia. Glacier change over the QTP has shown high temporal and spatial variability in recent decades, and the driving forces of the variability are not yet clear. This study examines the area and thickness change of glaciers in the Dongkemadi (DKMD) region over central QTP by exploring all available Landsat images from 1976 to 2013 and satellite altimetry data over 2003–2008, and then analyzes the relationships between glacier variation and local and macroscale climate factors based on various remote sensing and re-analysis data. Results show that the variation of glacier area over 1976–2013 is characterized by significant shrinkage at a linear rate of −0.31 ± 0.04 km2·year−1. Glacier retreat slightly accelerated in the 2000s, and the mean glacier surface elevation lowered at a rate of −0.56 m·year−1 over 2003–2008. During the past 38 years, glacier change in the DKMD area was dominated by the variation of mean annual temperature, and was influenced by the state of the North Atlantic Oscillation (NAO). The mechanism linking climate variability over the central QTP and the state of NAO is most likely via changes in the strength of westerlies and Siberian High. We found no evidence supporting the role of summer monsoons (Indian summer monsoon and East Asian monsoon) in driving local climate and glacier changes. In addition, El Niño Southern Oscillation (ENSO) may be associated with the extreme weather (snow storm) in October 1986 and 2000 which might have led to significant glacier expansion in the following years. Further research is needed to better understand the physical mechanisms linking NAO, ENSO and climate variability over the mid-latitude central QTP.