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Abstract Using an optimal detection technique and climate change simulations produced with two versions of two GCMs, we have assessed the causes of twentieth-century temperature changes from global to regional scales. Our analysis is conducted in nine spatial domains: 1) the globe; 2) the Northern Hemisphere; four large regions in the Northern Hemispheric midlatitudes covering 30°–70°N including 3) Eurasia, 4) North America, 5) Northern Hemispheric land only, 6) the entire 30°–70°N belt; and three smaller regions over 7) southern Canada, 8) southern Europe, and 9) China. We find that the effect of anthropogenic forcing on climate is clearly detectable at global through regional scales. The effect of combined greenhouse gases and sulfate aerosol forcing is detectable in all nine domains in annual and seasonal mean temperatures observed during the second half of the twentieth century. The effect of greenhouse gases can also be separated from that of sulfate aerosols over this period at continental and regional scales. Uncertainty in these results is larger in the smaller spatial domains. Detection is improved when an ensemble of models is used to estimate the response to anthropogenic forcing and the underlying internal variability of the climate system. Our detection results hold after removal of North Atlantic Oscillation (NAO)-related variability in temperature observations—variability that may or may not be associated with anthropogenic forcing. They also continue to hold when our estimates of natural internal climate variability are doubled.