In light of climate change, health risks are expected to be exacerbated by more frequent high temperatures and reduced by less frequent cold extremes. To assess the impact of different climate change scenarios, it is necessary to describe the current effects of temperature on health. A time-stratified case-crossover design fitted with conditional quasi-Poisson regressions and distributed lag non-linear models was applied to estimate specific temperature-mortality associations in nine urban agglomerations in Belgium, and a random-effect meta-analysis was conducted to pool the estimates. Based on 307,859 all-cause natural deaths, the mortality risk associated to low temperature was 1.32 (95% CI: 1.21–1.44) and 1.21 (95% CI: 1.08–1.36) for high temperature relative to the minimum mortality temperature (23.1 °C). Both cold and heat were associated with an increased risk of cardiovascular and respiratory mortality. We observed differences in risk by age category, and women were more vulnerable to heat than men. People living in the most built-up municipalities were at higher risk for heat. Air pollutants did not have a confounding effect. Evidence from this study helps to identify specific populations at risk and is important for current and future public health interventions and prevention strategies.