This investigation focused on the microstructural, workability, mechanical, and hyration evolution of blended cements composed of natural pozzolan with nanosilica (NS). In Turkey, the most common supplementary cementitious materials are natural pozzolans of volcanic origin. Volcanic pumice is a natural pozzolan produced by the release of gases during the cooling and solidification of lava. In this study, pumice powders with two different levels of fineness were used to replace ordinary portland cement (OPC) at 15%, 30%, and 45% by weight. Seven mixtures were proposed with different levels of pumice fineness and OPC replacement rates, as well as an additional control mixture without pumice powder. Companion mixtures were also produced by adding 3% NS (by total weight of cementitious materials) into the proposed mixtures for a total of 14 different mixtures. Fresh properties measured by flow test and mechanical performance validated by microstructural analyses show that in the presence of NS, up to 30% pumice powder can be replaced with OPC without risking workability and 2-day strength measurements. In cases where the early-age strength is necessary after the first 7 days, the same level of replacement can be increased up to 45%. The successful outcomes of this study may compensate for the drawbacks of OPC use in concrete mixtures and popularize the use of natural pozzolans in locations where they are more commonly available.