The study was conducted to assess time trend shifts of leading causes of death and their partial contributions over the years 1975–2016 in Spain. A longitudinal ecological epidemiologic design was conducted to analyse linear trend period shifts using joinpoint regression as the annual percentage of change (APC) in the period 1975–2016. The partial contributions were illustrated as the rate ratio of a singular-cause to their major-cause shift periods. HIV/AIDS shaped the increasing trend period of infectious diseases in 1989–1995 (APC = 25.3, P < 0.05) and the decreasing trend in 1995–1999 and 1999–2016. Lung cancer fell gradually from 1994 in men (−0.4, P < 0.05); however, in women, the condition continued increasing from 1990 (P < 0.05). Dementia types influenced mental and neurological disease drifts. The recent trend for circulatory periods (1980–2016) was mainly modulated by cardiac ischaemia, with increased partial contributions (25%, 32% and 30%). Traffic accidents defined the descending tendency of external causes. Spain showed a Western pattern in descended rates, including non-decreasing trends in mental and neurological diseases, pancreatic cancer, drug abuse and suicide. Trend shifts and partial contributions illustrated targets for further mortality reduction. Display omitted •The partial contributions of singular death causes allowed understanding mortality trends of their major causes of death.•Research on trend shifts of death causes is a toll for epidemiological surveillance and health policy tackling.•Mortality has been descending in Spain, except in mental and neurological diseases, and pancreatic cancer, drug abuse and suicide.