Using a three-dimensional global climate model, we show that mode-transitions in North Atlantic deep-water production can provide an amplifying mechanism of relatively weak climate perturbations during the Holocene. Under pre-industrial boundary conditions, a freshwater forcing in the Labrador Sea pushes the North Atlantic overturning circulation into a deterministically bistable regime, characterized by stochastic “on” and “off” switches in Labrador Sea convection. On a multicentennial time-scale these stochastic mode-transitions can be phase-locked by a small (subthreshold) periodic freshwater forcing. The local small periodic forcing is effectively amplified with the assistance of noise, to have a large-scale impact on North Atlantic overturning circulation and climate. These results suggest a stochastic resonance mechanism that can operate under Holocene boundary conditions and indicate that changes in the three-dimensional configuration of North Atlantic deep-water formation can be an important component of multicentennial climate variability during interglacials.