The dissertation addresses two "public health puzzles" in US mortality inequality trends: (1) SES inequalities in mortality have been growing wider despite declines in overall mortality levels and the expansion of social welfare policies; (2) mortality inequalities present diverging trends across age groups, with declines at younger ages but growth at older ages. These puzzles challenge existing theories in explaining the complex dynamics of mortality disparities. The study aims to bridge this gap by proposing an alternative theoretical framework that combines Fundamental Cause Theory with the concept of epidemiological transition.Previous research has focused primarily on socioeconomic factors as the main drivers of widening mortality disparities. However, this dissertation argues that mortality inequalities can evolve independently of socioeconomic factors due to shifts in disease patterns towards non-communicable diseases and advancements in health-beneficial innovations. By analyzing county-level US mortality rates from 1968 to 2020, this study reveals that mortality inequality related to infectious diseases declined in the early 1970s and remained stable over time. On the other hand, mortality inequality related to non-communicable diseases remained at a low level during the 1970s but saw a significant increase since the 1980s. Further, this study found that mortality inequality from non-communicable diseases is more pronounced in middle-aged and older adults, and the age distribution of mortality inequality progressively shifts towards older ages. This study contributes to the existing literature with a new theoretical perspective to understand the developments of mortality inequalities over time. This framework sheds light on the two "public health puzzles” and emphasizes the crucial role of disease patterns prevailing during specific historical periods in understanding the developments of mortality inequality. Furthermore, the study underlines the interplay of disease patterns, prevention/treatment innovations, and social and economic inequalities in collectively shaping the future of mortality and health disparities. It also sheds light on the social-political circumstances of medical innovation as well as behavioral factors over the life course in determining future population health and health inequalities.