Four thousand years ago what is often considered to be the world's first empire, the Akkadian Empire, collapsed. Proxy data has suggested a regional aridification event coincided with this collapse, but there is a lack of records collected from within the Mesopotamian region, where the Akkadian Empire was based. Here we analyse a suite of simulations from the HadCM3 climate model covering the last 6000 years. The results show that long-term drivers produced a shift to a more arid climate, showing minima in both precipitation and river flow at 2000 BCE, whilst temperatures were colder at 2250 BCE. These changes were sufficient to have a negative impact on the natural vegetation in Mesopotamia, suggesting that this climate change would have also impacted the agriculture sustaining local communities. We suggest that the combined effects of climate change and land mismanagement would lead to shortages of water and food, which may have contributed to social disruption and the collapse of the Akkadian Empire. We also find examples of resilience through the surviving cities such as Tell Brak and Tell Mozan. These could provide lessons for adapting to climate change in the future, as modern-day climate change threatens food and water security.