AbstractAmplified warming in the Mediterranean region in summer, corresponding to strengthening temperature seasonality (T_seasonality), increases the frequency and intensity of heatwaves and endangers both human health and ecosystems. However, previous studies have not found a detectable signal of anthropogenic forcing in changes in T_seasonality in the Mediterranean and the contribution from human activities is unclear. Here, we show that signals of anthropogenic forcing and greenhouse gas forcing can be detected for the period 1950–2014, the signals of anthropogenic and natural forcing are separable, and the contribution of anthropogenic forcing is 74% using the optimal fingerprinting approach. Future projections based on attribution constraints indicated that T_seasonality will continue to strengthen by more than 2°C by 2100, which is much worse than predicted by direct model output. These results are important for understanding and projecting the impacts of human activities on T_seasonality and related summer heatwaves in the future.