Cement kiln dust (CKD), which consisted of mullite, quartz, fused silica, and calcite (49, 23, 11 and 10 mass%, respectively) was alkali-activated ([NaOH]: 4–12 M) and cured under different conditions (25 ≤ T ≤ 85°C, time (t): up to 30 days). The microstructure of the cured samples was investigated using X-ray diffraction, Fourier-transform infrared spectroscopy and scanning electron microscopy. The mechanical/physical properties of the cured samples were related to the above factors using response surface methodology. The results showed that increasing the levels of these factors enhanced the reactivity of mullite and quartz, leading thus to the formation of hydrosodalite along with geopolymer. Conversely, a pseudo-amorphous phase along with limited amount of geopolymer occurred with lower levels of the factors. Moreover, samples prepared with concentrated solutions of NaOH or cured at high temperatures were the object of formation of zeolite ZK, and semi-crystallized hydroxysodalite, respectively. Tobermorite and hydroxysodalite were formed at long and short curing times, respectively. The mechanical/physical properties of the cured samples were well related to the operating factors through quadratic models, and their changes were discussed in relation to the microstructure characterization. The results of the desirability approach demonstrated that the optimal values for bending strength, compressive strength, porosity, and water absorption (10.4 MPa, 9.1 MPa, 16.4%, and 28%, respectively) are obtained at: [NaOH] = 10 M, T = 73°C, and t = 23 days. In the light of these results, the CKD is suitable as a binder for mortar and bricks.