Objectives We aim to understand how the second epidemiologic transition unfolded on the island of Newfoundland during the early 20th century. The focus is on changes in predominant causes of mortality throughout this period, urban and rural differences, and comparisons with other Western nations. We explore factors driving these patterns including the economy, nutrition, sanitation, and access to healthcare and discuss their relevance to understanding epidemiologic transitions in other developing regions. Methods We examined official provincial death records (n = 65,394) and census materials from 1900 to 1939 for three rural districts (Burgeo‐La Poile, Bonavista, and Twillingate) and the large city of St. John's. Life expectancies, infant mortality rates, survival curves, and proportionate mortality from communicable and non‐communicable diseases (NCDs) were calculated. RESULTS In all districts, old age mortality increased while infant and childhood mortality decreased, with corresponding increases in life expectancy. Proportionate mortality from communicable causes decreased while deaths from NCDs increased. These changes occurred earlier in urban St. John's than in outlying districts, suggesting rural–urban differences played a significant role in Newfoundland's second epidemiologic transition. However, the transition was significantly delayed relative to other Western nations. CONCLUSIONS We suggest that observed mortality patterns were the result of complex interactions between the poor economy, malnutrition, high prevalence of tuberculosis, and limited health and social services. These factors contribute to the delayed onset of the second epidemiologic transition in Newfoundland relative to other Western nations and the earlier onset in St. John's than in rural areas.