The southeast Tibetan Plateau has become the region with the fastest rate of mass loss within High Mountain Asia (HMA), and the mass loss from lake-terminating glaciers in the region is the most significant. However, the evolution of the mass change of lake-terminating glaciers is still unclear, and accurate penetration depth estimates of C-band and X-band radar in glacierized areas are unknown, which greatly hinders the monitoring and understanding of the glacier evolution. Hence, in this study, taking the largest lake-terminating glacier in HMA (the Yanong Glacier) as the study object, we first evaluated the X-band penetration depth using Pléiades and TanDEM-X data, and further combined the penetration depth difference between the C-band and X-band radar (1.14 ± 0.14 m) to estimate the C-band penetration depth based on a newly proposed area-weighted strategy, according to surface categories. The results indicate a region-wide average penetration depth of 1.84 ± 0.59 m and 2.98 ± 0.61 m for the X-band and C-band radar, respectively, demonstrating either an underestimation of 60% or an overestimation of 202% for the previous C-band penetration corrections. On this basis, we determined the multi-temporal glacier mass balance for the Yanong Glacier, using KH-9, SRTM DEM, SPOT-7, and multi-orbit TanDEM-X data. The results show that the Yanong Glacier has been in a state of serious mass loss (at a rate of −0.73 ± 0.13 m w.e./a) during 1974–2015, and the rate of mass loss has doubled since 2000 (i.e., −0.48 ± 0.20 (1974–2000), −0.95 ± 0.20 (2000−2012), and − 1.02 ± 0.53 m w.e./a (2012–2015)). Moreover, the inter-annual mass change has shown a highly volatile and accelerating trend during 2012–2015 (i.e., −0.47 ± 0.85 (2011−2012), −0.87 ± 0.66 (2012−2013), −1.26 ± 0.72 (2013–2014), and − 1.58 ± 0.44 m w.e./a (2014–2015)). By further analyzing the ERA5 reanalysis data and the changes in the proglacial lake and glacier dynamics, we can conclude that, qualitatively: 1) the long-term acceleration of mass loss at the Yanong Glacier has mainly been controlled by climate change, but has also been affected by the glacier dynamics to a limited extent; and 2) the inter-annual acceleration of mass loss has, to some extent, been affected by subglacial/englacial melting. The findings of this study will not only provide an accurate penetration depth correction for future relevant studies, but will also significantly improve the understanding of the evolution of lake-terminating glaciers in HMA and other high mountain areas of the world.