As an important way of maximizing land productivity by growing more than one crop type in the same field, mixed cropping has been an effective option for sustaining population growth under different climatic conditions since prehistoric period. We used a combination of archaeological data and an improved prehistoric land use model (PLUM) to quantitatively reconstruct spatiotemporal changes in cropland types and areas in the Huai River Valley of China, a core region of mixed cropping during the Holocene. The total cropland area increased more than 25 times during 8–2 ka BP, with northward expansion of rice-dominated cultivation during 5–4 ka BP and southward expansion of dry-dominated cultivation after 4 ka BP. Temperature and precipitation determined cropland types distribution, while that of cropland area was controlled by cultural development. The interplay between past climate, culture, and cultivation potentially provides useful insights into mitigating future population pressures with climate change.