This paper presents the investigations of selected properties of concrete containing two fractions of fly ash microspheres (FAMs) with grain size up to 200 µm and up to 500 µm. Concrete mixtures with ordinary Portland cement and three substitution rates of cement by FAMs, 1.3%, 2.0%, and 2.6%, were investigated. For all concrete mixes, the constant water–binder ratio (w/b) equal to 0.50 was used. The research program included the determination of chemical composition, particle size distribution, and pozzolanic activity of FAMs. The analysis showed that the microspheres consist of three main elements: silicon, aluminum, and iron, whose oxides constitute about 89% of the material. The total content of air pores, measured in concrete at 28 days, ranges from 1.3 to 3.1% for the grain sizes below 200 µm and from 1.4% to 3.9% for the grain sizes up to 500 µm. The FAMs with a particle diameter < 200 µm have a relatively high level of activity pozzolanic at 28 days. The SEM analysis proved that the use of microspheres reduces gaps and increases the CSH phase. The compression test showed that the addition of fly ash microspheres with grain size below 200 µm increases long-term concrete strength.