Northwestern Alaska has been highly affected by changing climatic patterns with new temperature and precipitation maxima over the recent years. In particular, the Baldwin and northern Seward peninsulas are characterized by an abundance of thermokarst lakes that are highly dynamic and prone to lake drainage like many other regions at the southern margins of continuous permafrost. We used Sentinel-1 synthetic aperture radar (SAR) and Planet CubeSat optical remote sensing data to analyze recently observed widespread lake drainage. We then used synoptic weather data, climate model outputs and lake ice growth simulations to analyze potential drivers and future pathways of lake drainage in this region. Following the warmest and wettest winter on record in 2017/2018, 192 lakes were identified as having completely or partially drained by early summer 2018, which exceeded the average drainage rate by a factor of ∼ 10 and doubled the rates of the previous extreme lake drainage years of 2005 and 2006. The combination of abundant rain- and snowfall and extremely warm mean annual air temperatures (MAATs), close to 0 ∘C, may have led to the destabilization of permafrost around the lake margins. Rapid snow melt and high amounts of excess meltwater further promoted rapid lateral breaching at lake shores and consequently sudden drainage of some of the largest lakes of the study region that have likely persisted for millennia. We hypothesize that permafrost destabilization and lake drainage will accelerate and become the dominant drivers of landscape change in this region. Recent MAATs are already within the range of the predictions by the University of Alaska Fairbanks' Scenarios Network for Alaska and Arctic Planning (UAF SNAP) ensemble climate predictions in scenario RCP6.0 for 2100. With MAAT in 2019 just below 0 ∘C at the nearby Kotzebue, Alaska, climate station, permafrost aggradation in drained lake basins will become less likely after drainage, strongly decreasing the potential for freeze-locking carbon sequestered in lake sediments, signifying a prominent regime shift in ice-rich permafrost lowland regions.