The Arctic environmental change is of global ecological and socio-economic relevance. Permafrost processes are key drivers of Arctic terrestrial ecosystems and they are crucial to understand the regional landscape evolution. This study provides insights into past landscape dynamics on the Seward Peninsula in Northwest Alaska (U.S.A.) based on sediment cores from drained lake basins. A multi-proxy approach is applied covering methods of sedimentology, biogeochemistry, geochronology, and micropaleontology (ostracoda, testate amoeba) to understand the formation and demise of the former thermokarst lake and its deep basin as a typical example for thermokarst systems in vast Arctic lowlands. Thermokarst can be triggered but also interrupted by global climate change (e.g. rapid warming and wetting in the Early Holocene), regional environmental change (e.g. due to nearby volcanic eruptions and tephra deposition) or local disturbance processes (e.g. lake drainage). We found that the development of a drained lake basin can undergo several cycles of aquatic and terrestrial phases. The investigated basin started as a Mid-Wisconsin wetland developing on an ice-rich permafrost terrain about 45,000 years before present. The potential initial lake evolution during a wetter interstadial phase in the Late Pleistocene was disturbed by falling of a thick volcanic tephra about 40,000 years before present associated with a phreatomagmatic eruption of a nearby Maar lake. Loess-like sedimentation and aggradation of ice-rich permafrost occurred during the following stadial period. By about 300 years before present a new thaw lake developed at our study site and expanded rapidly to a basin 20 m deep and 500 m x 300 m wide. The lake drained recently in the early 2000`s and permafrost started reforming again. The presented study demonstrates how active and dynamic but also how sensitive periglacial landscapes are – in the past, present and most possibly in the future. This needs to be considered when discussing our “anthropocene” future in the framework of climate change.