To study the combination principles of structural design and material design in asphalt pavement with semi-rigid bases, the software BISAR3.0 was used to analyze the load responses in asphalt pavement with two layers of semi-rigid base courses, and its inversed structure. Then composite beam specimens composed of two kinds of cement-treated macadam with different cement contents were then fabricated, and four-point bending strength and fatigue tests were conducted. Results indicated that the lower semi-rigid base layer (lower base) undertakes greater tensile stress than the upper semi-rigid base layer (upper base), and the fatigue life of the pavement structure is dependent on the lower base. Therefore, using inferior materials for the lower base and superior materials for the upper base is unreasonable. The inversed structure can fully utilize each material, and its bearing capacity and fatigue resistance were considerably improved. Thus, pavement structural design should be combined with material design according to the tensile stress state in pavement layers.