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The A’nyêmaqên Mountains have the largest concentration of glaciers in the Yellow River basin, which play a crucial role in regulating the runoff regime of the Yellow River. Thus, the quantification of glacier mass balance and its effects on river runoff is greatly required. However, current studies mainly focus on mass changes since 2000. Here, we report for the first time region-wide glacier elevation and mass changes, which were derived from digital elevation models (DEMs) produced from historical topographic maps (TOPO), SRTM retrievals, and ASTER L1A stereo imagery spanning the past 50 years. The results indicated a negative mass balance (−0.24 ± 0.05 m w.e. a⁻¹) of all glaciers for the 1966–2018 timespan. The mass loss rapidly accelerated from −0.16 ± 0.09 m w.e. a⁻¹ in 1966–2000 to −0.36 ± 0.06 m w.e. a⁻¹ during the period from 2000–2018. The rise in mass loss rate from 2000 onwards was mainly associated with the rapidly increased summer warming.