This study conducted a detection and attribution analysis of the observed global and regional changes in extreme temperatures during 1951–2015. HadEX3 observations were compared with multimodel simulations from the Coupled Model Intercomparison Project phase 6 (CMIP6) using an optimal fingerprinting technique. Annual maximum daily maximum and minimum temperatures (TXx and TNx; warm extremes) and annual minimum daily maximum and minimum temperatures (TXn and TNn; cold extremes) over land were analyzed considering global, continental, and subcontinental scales. Response patterns (fingerprints) of extreme temperatures to anthropogenic (ANT), greenhouse gases (GHG), aerosols (AA), and natural (NAT) forcings were obtained from CMIP6 forced simulations. The internal variability ranges were estimated from preindustrial control simulations. A two-signal detection analysis where the observations are regressed onto ANT and NAT fingerprints simultaneously reveals that ANT signals are robustly detected in separation from NAT over global and all continental domains (North and South America, Europe, Asia, and Oceania) for most of the extreme indices. ANT signals are also detected over many subcontinental regions, particularly for warm extremes (more than 60% of 33 subregions). A three-signal detection analysis that considers GHG, AA, and NAT fingerprints simultaneously demonstrates that GHG signals are detected in isolation from other external forcings over global, continental, and several subcontinental domains especially for warm extremes, explaining most of the observed warming. Moreover, AA influences are detected for warm extremes over Europe and Asia, indicating significant offsetting cooling contributions. Overall, human influences are detected more frequently, compared to previous studies, particularly for cold extremes, due to the extended period and the improved spatial coverage of observations.