Thermokarst lakes are widespread in Arctic lowlands. Under a warming climate, landscapes with highly ice-rich Yedoma Ice Complex (IC) deposits are particularly vulnerable, and thermokarst lake area dynamics serve as an indicator for their response to climate change. We conducted lake change trend analysis for a 44,500 km2 region of the Kolyma Lowland using Landsat imagery in conjunction with TanDEM-X digital elevation model and Quaternary Geology map data. We delineated yedoma–alas relief types with different yedoma fractions, serving as a base for geospatial analysis of lake area dynamics. We quantified lake changes over the 1999–2018 period using machine-learning-based classification of robust trends of multi-spectral indices of Landsat data and object-based long-term lake detection. We analyzed the lake area dynamics separately for 1999–2013 and 1999–2018 periods, including the most recent five years that were characterized by very high precipitation. Comparison of drained lake basin area with thermokarst lake extents reveal the overall limnicity decrease by 80% during the Holocene. Current climate warming and wetting in the region led to a lake area increase by 0.89% for the 1999–2013 period and an increase by 4.15% for the 1999–2018 period. We analyzed geomorphological factors impacting modern lake area changes for both periods such as lake size, elevation, and yedoma–alas relief type. We detected a lake area expansion trend in high yedoma fraction areas indicating ongoing Yedoma IC degradation by lake thermokarst. Our concept of differentiating yedoma–alas relief types helps to characterize landscape-scale lake area changes and could potentially be applied for refined assessments of greenhouse gas emissions in Yedoma regions. Comprehensive geomorphological inventories of Yedoma regions using geospatial data provide a better understanding of the extent of thermokarst processes during the Holocene and the pre-conditioning of modern thermokarst lake area dynamics.