Turbulent socio-economic development, recent political challenges, and remarkable regional diversity with deep historical roots make Ukraine an important case study for understanding mortality trends in Eastern Europe. In this paper, we provide the first comprehensive, spatially detailed analysis of cause-specific mortality trends and patterns in Ukraine, focusing on the period 2006–19. We rely on official mortality data and use various demographic and spatial analysis techniques. Our results suggest a notable attenuation of the long-standing West–East and West–South–East mortality gradients. Cardiovascular mortality at older ages largely explains the gap between the vanguard (lowest mortality) and laggard (highest mortality) areas, especially for females and in the most recent period. By contrast, the impact of mortality from external causes has greatly diminished over time. Hotspot analyses reveal strong and persistent clustering of mortality from suicide, HIV, and lung cancer. Further research should focus on in-depth assessment of the mechanisms causing the observed patterns.