The temporal and spatial slopes of water isotope‐temperature relations are studied for the last 21,000 years over the middle and high latitudes using a series of snapshot simulations of global climate and water isotopes in the isotope‐enabled atmospheric model isoCAM3. Our model simulation suggests that both the temporal slope and spatial slope remain largely stable throughout the last deglaciation. Furthermore, the temporal slope can vary substantially across regions. Nevertheless, on average, and most likely, the temporal slope is about 0.3‰ °C−1 and is about half of the spatial slope. Finally, the relation between temporal and spatial slopes is understood using a semiempirical equation that is derived based on both the Rayleigh distillation and a fixed spatial slope. The slope equation quantifies the Boyle's mechanism and suggests that the temporal slope is usually smaller than the spatial slope in the extratropics mainly because of the polar amplification feature in global climate change, such that the response in local temperature at middle and high latitudes is usually greater than that in the total equivalent source temperature.