The degree to which population vulnerability to outdoor temperature is reduced by improvements in infrastructure, technology, and general health has an important bearing on what realistically can be expected with future changes in climate. Using autoregressive Poisson models with adjustment for season, the authors analyzed weekly mortality in London, United Kingdom, during four periods (1900-1910, 1927-1937, 1954-1964, and 1986-1996) to quantify changing vulnerability to seasonal and temperature-related mortality throughout the 20th century. Mortality patterns showed an epidemiologic transition over the century from high childhood mortality to low childhood mortality and towards a predominance of chronic disease mortality in later periods. The ratio of winter deaths to nonwinter deaths was 1.24 (95% confidence interval (CI): 1.16, 1.34) in 1900-1910, 1.54 (95% CI: 1.42, 1.68) in 1927-1937, 1.48 (95% CI: 1.35, 1.64) in 1954-1964, and 1.22 (95% CI: 1.13, 1.31) in 1986-1996. The temperature-mortality gradient for cold deaths diminished progressively: The increase in mortality per 1 degree C drop below 15 degrees C was 2.52% (95% CI: 2.00, 3.03), 2.34% (95% CI: 1.72, 2.96), 1.64% (1.10, 2.19), and 1.17% (95% CI: 0.88, 1.45), respectively, in the four periods. Corresponding population attributable fractions were 12.5%, 11.2%, 8.7%, and 5.4%. Heat deaths also diminished over the century. There was a progressive reduction in temperature-related deaths over the 20th century, despite an aging population. This trend is likely to reflect improvements in social, environmental, behavioral, and health-care factors and has implications for the assessment of future burdens of heat and cold mortality.