Climate change looms as the biggest threat of the 21st century, and its effect on urban mortality is exacerbated by urban heat islands. This study analyzes the impact of high temperatures, heatwaves, and the urban heat island on the cardiovascular and respiratory mortality of people over 65 years of age for the years 2002 to 2012. The area of application is Athens, Greece, an urban agglomeration experiencing an urban heat island of high intensity. The correlation of the daily cardiovascular and respiratory mortality count of people over 65 years of age with various temperature measures confirmed a U-shaped exposure response curve, with fewer deaths in the range of moderate temperatures. At high and very high temperatures, this mortality increased by 20% to 35% correspondingly, at a 99.9% significance level. Mortality was further investigated with ordinary least squares, Poisson, and negative binomial times series models, which, although suffering from poor fit, showed a one-day lag for the maximum temperature effect on mortality. Finally, cluster analysis for observations confined to May to September, confirmed by multiple discriminant analysis, showed the existence of six clusters, with the highest excess mortality count of 23% for the cluster that included the hottest days and 20.6% for the heatwave cluster. To this end, it is recommended that policies target high ambient temperatures and heatwaves as a priority.