Sea-level rise due to ice loss in the Northern Hemisphere in response to insolation and greenhouse gas forcing is thought to have caused grounding-line retreat of marine-based sectors of the Antarctic Ice Sheet (AIS)1,2,3. Such interhemispheric sea-level forcing may explain the synchronous evolution of global ice sheets over ice-age cycles. Recent studies that indicate that the AIS experienced substantial millennial-scale variability during and after the last deglaciation4,5,6,7 (roughly 20,000 to 9,000 years ago) provide further evidence of this sea-level forcing. However, global sea-level change as a result of mass loss from ice sheets is strongly nonuniform, owing to gravitational, deformational and Earth rotational effects8, suggesting that the response of AIS grounding lines to Northern Hemisphere sea-level forcing is more complicated than previously modelled1,2,6. Here, using an ice-sheet model coupled to a global sea-level model, we show that AIS dynamics are amplified by Northern Hemisphere sea-level forcing. As a result of this interhemispheric interaction, a large or rapid Northern Hemisphere sea-level forcing enhances grounding-line advance and associated mass gain of the AIS during glaciation, and grounding-line retreat and mass loss during deglaciation. Relative to models without these interactions, the inclusion of Northern Hemisphere sea-level forcing in our model increases the volume of the AIS during the Last Glacial Maximum (about 26,000 to 20,000 years ago), triggers an earlier retreat of the grounding line and leads to millennial-scale variability throughout the last deglaciation. These findings are consistent with geologic reconstructions of the extent of the AIS during the Last Glacial Maximum and subsequent ice-sheet retreat, and with relative sea-level change in Antarctica3,4,5,6,7,9,10.