A multiproxy sedimentary record from Lake Igaliku in southern Greenland documents 1450 years of human impacts on the landscape. Diatoms, scaled chrysophytes, and C and N geochemistry show perturbations consistent with recent agricultural activities (post-ad 1980), superimposed upon long-term environmental variability. While the response to Norse agriculture (~ad 986-1450) is weak, the biological response to the last 30 years of modern sheep farming is marked, with drastic changes in diatom taxa, δ13C and δ15N isotopic ratios, and a sharp increase in scaled chrysophytes. Indeed, current conditions in the lake during the last 30 years are unprecedented in the context of the last 1450 years. The dominant driver for recent changes is likely an intensification of agricultural practices combined with warming summer temperatures. Warm temperatures and agricultural disturbance together during Norse Landnám did not lead to the marked changes seen in the modern lake environment over the last 30 years. The synergistic response between increased climate warming and agriculture will likely have unanticipated effects. These findings confirm the sensitivity of Arctic lakes to external anthropogenic forcing and are the first analyses of their kind for the effects of agriculture in Greenland.