Numerical simulations allow us to gain a comprehensive understanding of the underlying mechanisms of past, present, and future climate changes. The mid-Holocene (MH) and the last interglacial (LIG) were the two most recent warm episodes of Earth’s climate history and are the focus of paleoclimate research. Here, we present results of MH and LIG simulations with two versions of the state-of-the-art Earth system model AWI-ESM. Most of the climate changes in MH and LIG compared to the preindustrial era are agreed upon by the two model versions, including 1) enhanced seasonality in surface temperature that is driven by the redistribution of seasonal insolation; 2) a northward shift of the intertropical convergence zone (ITCZ) and tropical rain belt; 3) a reduction in annual mean Arctic sea ice concentration; 4) weakening and northward displacement of the Northern Hemisphere Hadley circulation, which is related to the decrease and poleward shift of the temperature gradient from the subtropical to the equator in the Northern Hemisphere; 5) a westward shift of the Indo-Pacific Walker circulation due to anomalous warming over the Eurasia and North Africa during boreal summer; and 6) an expansion and intensification of Northern Hemisphere summer monsoon rainfall, with the latter being dominated by the dynamic component of moisture budget (i.e., the strengthening of wind circulation). However, the simulated responses of the Atlantic meridional overturning circulation (AMOC) in the two models yield different results for both the LIG and the MH. AMOC anomalies between the warm interglacial and preindustrial periods are associated with changes in North Atlantic westerly winds and stratification of the water column at the North Atlantic due to changes in ocean temperature, salinity, and density.