Fatigue cracking in asphalt mixtures—a common, widely studied mode of distress in flexible pavements—necessitates major investments in pavement maintenance and rehabilitation. To date, research has focused on the response of bituminous mixes subjected to cyclic loading until failure. Moreover, low-temperature thermal stresses in bituminous mixes have been investigated in isolation to determine the effect of thermal gradients on materials. However, decreased temperature leads to a combined effect of fatigue distress and thermal stress. To provide insight into this phenomenon, an experimental study based on a new test procedure developed by the Road Research Laboratory of the Technical University of Catalonia, Spain, is presented. This method allows the simultaneous evaluation of the effect of thermal stresses and the fatigue response of asphalt mixtures.