The poor natural regeneration of Pinus koraiensis is a key limitation for restoring the primary mixed Pinus koraiensis forests. Seed harvesting and climate change are the important factors that influence the natural regeneration of Pinus koraiensis; however, it is hard to illustrate how, in synergy, they affect its regeneration at the landscape scale. In this study, we coupled an ecosystem process model, LINKAGES, with a forest landscape model, LANDIS PRO, to evaluate how seed harvesting and climate change influenced the natural regeneration of Pinus koraiensis over large temporal and spatial scales. Our results showed that seed harvesting decreased the abundance of Pinus koraiensis juveniles by 1, 14, and 18 stems/ha under the historical climate, and reduced by 1, 17, and 24 stems/ha under the future climate in the short- (years 0–50), medium- (years 60–100), and long-term (years 110–150), respectively. This indicated that seed harvesting intensified the poor regeneration of Pinus koraiensis, irrespective of climate change. Our results suggested that seed harvesting diminished the generation capacity of Pinus koraiensis over the simulation period. Seed harvesting reduced the abundance of Pinus koraiensis at the leading edge and slowed down its shift into high-latitude regions to adapt to climate change. Our results showed that the effect magnitudes of seed harvesting, climate change, their interaction and combination at the short-, medium- and long-term were −61.1%, −78.4%, and −85.7%; 16.5%, 20.9%, and 38.2%; −10.1%, −16.2% and −32.0%; and −54.7%, −73.8%, and −79.5%, respectively. Seed harvesting was a predominant factor throughout the simulation; climate change failed to offset the negative effect of seed harvesting, but the interactive effect between seed harvesting and climate change almost overrode the positive effect of climate change. Seed harvesting, climate change, and their interaction jointly reduced the natural regeneration of Pinus koraiensis. We suggest reducing the intensity of seed harvesting and increasing silvicultural treatments, such as thinning and artificial plantation, to protect and restore the primary mixed Pinus koraiensis forests.