The warm-temperate regions of the globe characterized by dry summers and wet winters (Mediterranean climate; MED) are especially vulnerable to climate change. The potential impact on water resources, ecosystems and human livelihood requires a detailed picture of the future changes in this unique climate zone. Here we apply a probabilistic approach to quantitatively address how and why the geographic distribution of MED will change based on the latest-available climate projections for the 21st century. Our analysis provides, for the first time, a robust assessment of significant northward and eastward future expansions of MED over both the Euro-Mediterranean and western North America. Concurrently, we show a significant 21st century replacement of the equatorward MED margins by the arid climate type. Moreover, future winters will become wetter and summers drier in both the old and newly established MED zones. Should these projections be realized, living conditions in some of the most densely populated regions in the world will be seriously jeopardized.