The High Arctic plays a vital role in Earth's climate system, and its ecosystems are highly sensitive to global climate change. High Arctic lakes are valuable sentinels of climate change, as their sediments integrate long-term natural climatic fluctuations and anthropogenic influences. Here, we present a high-resolution ∼5000 year-reconstruction of NE Greenland climate variability from Aucella Lake (74°N, 20°E) based on physical, chemical, and biological properties of lake sediments. We use CT-scans, hyperspectral imaging, organic matter, XRD, and diatom analyses to show that changing air temperatures were controlled by a mix of regional climatic changes and local landscape feedbacks. The latest Mid-Holocene (∼5.0–3.8 cal. ka BP) was characterized by relatively warmer conditions, while the onset of the Late-Holocene was marked by abrupt temperature decreases that coincided with the beginning of glacial advances elsewhere (∼3.8–3.4 cal. ka BP). From ∼3.4–2.4 cal. ka BP, the sedimentary record indicated progressive warming, with temperature peaking during the Medieval Climate Anomaly, although temperature rises were punctuated by abrupt, short-lived cold periods. From ∼1.1–0.05 cal. ka BP, the influence of landscape factors over the system diminished. Sedimentary indicators suggested a transition towards a colder, more humid climate, coinciding with the beginning of the Little Ice Age, that was characterized by a marked decrease in air temperature that reached minimum values at the end of this period. The last 50 years at Aucella Lake were marked by abrupt temperature rises, consistent with recently observed anthropogenic global warming. Our results illustrate the importance of high-resolution multiproxy studies for accurately characterizing lake linkages to their environment and climate.