Although climate change and the expansion of agriculture are two of the primary threats to global biodiversity, they are usually considered independently. Here, I show that climate change and agricultural expansion interact synergistically in their impacts on mammals across mega-biodiverse Southeast Asia. Rising temperatures do not directly reduce niche availability for most species but do trigger a major altitudinal expansion in the cultivation zone for oil palm (Elaeis guineensis), a cold-intolerant crop tree that is currently restricted to tropical lowlands. The resulting replacement of native forests would reduce mammal ranges by 47-67% by 2070, given a low-or high-carbon-emissions trajectory, respectively. This reduction is 3-4 times the magnitude of that predicted from land-use change without considering climatic effects. The synergistic interaction between climate change and land-use change greatly outweighs the impact on biodiversity of either factor alone or their additive combination.