The dynamics of glaciers serve as one of the most important indicators of climate change. Whilst current research has primarily concentrated on long-term interannual glacier mass balance and its response to climate change, glaciers may respond more rapidly to climate change, highlighting the urgent need for intra-annual mass balance estimations. Investigating seasonal or short-term variations in glacier mass balance not only enhances our understanding of the interactions between glaciers and the climate system but also provides crucial data for water resource management and ecological protection. The ICESat-2 and NASADEM datasets were used to estimate the inter- and intra-annual glacier mass balance changes in the mid-latitude Eurasia from 2019 to 2022. Additionally, the response of glacier mass balance to regional air temperature and precipitation values was analysed using ERA5-Land data and multiple regression analysis, respectively. From 2019 to 2022, glacier mass loss in mid-latitude Eurasia reached −45.02 ± 34.21 Gt per year, contributing to a global sea-level rise of 0.12 ± 0.09 mm per year. The glacier melt rate in the study area from 2019 to 2022 was 2.33 times higher than that from 2000 to 2019. With the exception of the Western Kunlun region, which experienced a weak accumulation rate of 0.04 ± 0.35 m w.e. per year, all other areas experienced ablation states. Seasonal mass balance responds differently to temperature and precipitation variations across seasons: higher temperatures in different seasons lead to more negative mass balances, while increased winter and spring precipitation can slow down glacier melt. Air temperature dominates the glacier mass balance changes in the study area. The intense heat in 2022 raised average glacier temperatures by 1.04 °C compared to 2019–2021, resulting in a more negative mass balance and an increased ice loss of −0.34 ± 1.01 m w.e. per year (−35.07 ± 103.22 Gt per year). This analysis indicates that glacier mass balance is highly sensitive to climate change, even on a seasonal scale. Moreover, the high precision and spatiotemporal resolution ICESat-2 data can facilitate the investigation of large-scale glacier mass balance on short time scales.