Since the 1970s it has been recognised that Southern Hemisphere samples have a lower radiocarbon content than contemporaneous material in the Northern Hemisphere. This interhemispheric radiocarbon offset has traditionally been considered to be the result of a greater surface area in the southern ocean and high-latitude deepwater formation. This is despite the fact that the El Niño–Southern Oscillation (ENSO) is known to play a significant role in controlling the interannual variability of atmospheric carbon dioxide by changing the flux of ‘old’ CO2 from the tropical Pacific. Here we demonstrate that over the past millennium, the Southern Hemisphere radiocarbon offset is characterised by a pervasive 80-yr cycle with a step shift in mean values coinciding with the transition from the Medieval Warm Period to the Little Ice Age. The observed changes suggest an ENSO-like role in influencing the interhemispheric radiocarbon difference, most probably modulated by the Interdecadal Pacific Oscillation, and supports a tropical role in forcing centennial-scale global climate change.