We stratified the Italian population according to age and gender in order to evaluate mortality trends over more than one century. Data covering the 1901-2008 period were used to study the yearly variations in mortality. Fluctuations in age-adjusted mortality curves were analyzed by Join Point Regression Models, identifying Join Points and Annual Percent Changes. A consistent decline in all-cause mortality occurred across the whole period, the most striking variations being observed in the 0-49 years population. In 1901, other and undefined diseases were the main causes of death, followed by infectious, digestive, and respiratory diseases in the 0-49 years population and by respiratory, cardiovascular, and cerebrovascular diseases in the ≥ 50 years population groups. In 2008 the main causes of death were accidents (males) and tumors (females) in the 0-49 age class, tumors in the 50-69 age class (both genders), and tumors (males) and cardiovascular diseases (females) in the elderly. The results highlight the interplay between age and gender in affecting mortality trends and reflect the dramatic progress in nutritional, lifestyle, socioeconomic, medical, and hygienic conditions.