This paper documents the use of an isothermal calorimeter as a scanning tool to evaluate early-age behavior of high-volume fly ash mixtures. A series of paste and mortar mixtures containing different fly ashes (one Class C fly ash and two Class F fly ashes) with replacement levels ranging from 20% to 60% and high- and low-alkali cement was evaluated. Materials testing included ASTM C109, compressive strength of mortar cubes at different ages; ASTM C1437, flow; ASTM C403, time of setting; and ASTM C1679, isothermal calorimetry. In most cases, for the same water–binder ratio (0.40) and replacement level, Class C fly ash mixtures exhibited higher strength but delayed setting compared with Class F fly ash mixtures. Isothermal calorimetry proved to be a good scanning tool for predicting setting time and early-age compressive strength and for identifying materials incompatibility.