While regional mortality inequalities in Germany tend to be relatively stable in the short run, over the course of the past century marked changes have occurred in the country’s regional mortality patterns. These changes include not only the re-emergence of stark differences between eastern and western Germany after 1970, which have almost disappeared again in the decades after Germany’s unification in 1990; but also substantial changes in the patterns in northern and southern Germany. By the end of the 19th century, the northern regions in Germany had the highest life expectancy levels, while the southern regions had the lowest. Today, this mortality pattern is reversed. In this paper, we study these long-term trends in spatial mortality disparities in Germany since 1900, and link them with theoretical considerations and existing research on the possible determinants of these pattern. Our findings support the view that the factors which contributed to shape spatial mortality variation have changed substantially over time, and suggest that the link between regional socioeconomic conditions and mortality outcomes strengthened over the last 100 years.