The giant deer, Megaloceros giganteus, is one of the most celebrated of late Quaternary megafaunal species. Here we present new radiocarbon data on the pattern of its extinction, and compare this, on a region-by-region basis, with evidence of environmental change and human occupation. Following strict auditing criteria for the acceptance of radiocarbon dates, 51 dates are published here for the first time, bringing the total number of accepted dates for the species to 134. For western Europe, extirpation around the start of the Younger Dryas stadial is corroborated. Previous early-to mid-Holocene records for the Urals and Siberia are augmented by new dates that together provide an almost continuous radiocarbon record from the late-glacial to the mid-Holocene. Newly-rediscovered skeletal material of giant deer from the Maloarchangelsk region of European Russia has provided the latest date for the species known so far, and extends the mid-Holocene range substantially westward almost to Ukraine. The relatively narrow overall distribution of M. giganteus through its history, and direct palaeoecological evidence, demonstrate the species’ requirement for a mixed, partially open habitat providing both graze and browse. Its extirpation from western Europe remains strongly linked to deterioration of climate and productivity in the Younger Dryas, while its disappearance from more eastern areas correlates chronologically with the spread of closed forest. However, these intervals also coincide with the arrival of (probably sparse) human populations in the regions occupied by giant deer in Ireland and across Russia. The pattern of distributional changes leading to the Holocene restriction of giant deer populations strongly suggests environmental causation, but a contribution of human hunting to the extirpation of terminal populations cannot be ruled out.