Male excess mortality is mostly related to non-biological factors, and is thus of high social- and health-policy concern. Previous research has mainly focused on national patterns, while subnational disparities have been less in the focus. This study takes a spatial perspective on subnational patterns, covering seven European countries at the crossroad between Eastern and Western Europe. We analyze a newly gathered spatially detailed data resource comprising 228 regions with well-established demographic methods to assess the contribution of specific causes of death to the evolution of sex mortality differentials (SMDs) since the mid-1990s. Our results show that declines in SMDs were mostly driven by a reduction of male excess mortality from cardiovascular diseases and neoplasms (about 50–60% and 20–30%, respectively). In Western Europe, trends in deaths from neoplasms contributed more to the reduction of SMDs, while among regions located in Eastern-Central Europe narrowing SMDs were mostly driven by changes in cardiovascular disease-related deaths. Moreover, men show up to three times higher mortality levels from external causes as compared to women in several analyzed regions. But in absolute terms, external deaths play only a minor role in explaining SMDs due to their small contribution to overall mortality. We conclude that examining the regional development of SMDs is useful for introducing targeted social and health policies in order to reduce and prevent mortality inequalities between women and men.