Cement production in the world market is steadily increasing. In 2000, it was 1600 million tons, while as of 2013, the annual amount exceeded 4000 million tons. The burning of cement clinker is associated with the generation of waste. It is estimated that the amount of cement kiln dust (CKD), during combustion, reaches about 15–20%, which means 700 million tons per year. However, not all types of by-products are reusable due to high alkali, sulfate, and chloride contents, which can adversely affect the environment. One environmentally friendly solution may be to use CKD in the production of high-performance concrete (HPC), as a substitute for some of the cement. This paper presents a study of the short- and long-term physical and mechanical properties of HPC with 5%, 10%, 15%, and 20% CKD additives. The experiments determined density, water absorption, porosity, splitting tensile strength, compressive strength, modulus of elasticity, ultrasonic pulse velocity, and evaluated the microstructure of the concrete. The addition of CKD up to 10% caused an increase in the 28- and 730-day compressive strengths, while the values decreased slightly when CKD concentration increased to 20%. Splitting tensile strength decreased proportionally with 5–20% amounts of CKD regardless of HPC age. Porosity, absorbability, and ultrasonic pulse velocity decreased with increasing cement dust, while the bulk density increased for HPC with CKD. Microstructure analyses showed a decrease in the content of calcium silicate hydrate (C–S–H), acceleration of setting, and formation of wider microcracks with an increase in CKD. From the results, it was shown that a 15% percentage addition of CKD can effectively replace cement in the production of HPC and contribute to reducing the amount of by-product from the burning of cement clinker.