The growth and reduction of Northern Hemisphere ice sheets over the past million years is dominated by an approximately 100,000-year periodicity and a sawtooth pattern1,2 (gradual growth and fast termination). Milankovitch theory proposes that summer insolation at high northern latitudes drives the glacial cycles3, and statistical tests have demonstrated that the glacial cycles are indeed linked to eccentricity, obliquity and precession cycles4,5. Yet insolation alone cannot explain the strong 100,000-year cycle, suggesting that internal climatic feedbacks may also be at work4,5,6,7. Earlier conceptual models, for example, showed that glacial terminations are associated with the build-up of Northern Hemisphere ‘excess ice’5,8,9,10, but the physical mechanisms underpinning the 100,000-year cycle remain unclear. Here we show, using comprehensive climate and ice-sheet models, that insolation and internal feedbacks between the climate, the ice sheets and the lithosphere–asthenosphere system explain the 100,000-year periodicity. The responses of equilibrium states of ice sheets to summer insolation show hysteresis11,12,13, with the shape and position of the hysteresis loop playing a key part in determining the periodicities of glacial cycles. The hysteresis loop of the North American ice sheet is such that after inception of the ice sheet, its mass balance remains mostly positive through several precession cycles, whose amplitudes decrease towards an eccentricity minimum. The larger the ice sheet grows and extends towards lower latitudes, the smaller is the insolation required to make the mass balance negative. Therefore, once a large ice sheet is established, a moderate increase in insolation is sufficient to trigger a negative mass balance, leading to an almost complete retreat of the ice sheet within several thousand years. This fast retreat is governed mainly by rapid ablation due to the lowered surface elevation resulting from delayed isostatic rebound14,15,16, which is the lithosphere–asthenosphere response. Carbon dioxide is involved, but is not determinative, in the evolution of the 100,000-year glacial cycles.