Fly ash and slag are widely used in cement production. The effect of alkali sulfates in clinker on hydration and hardening of cement blended with fly ash and slag is studied. The results of hydration heat evolution, hydrates analysis and mechanical properties indicate arcanite (K2SO4), thenardite (Na2SO4), aphthitalite (3K2SO4·Na2SO4, K3NS4) and Ca-langbeinite (K2SO4·2CaSO4, KC2S3) in clinker could activate the pozzolanic activity of fly ash and slag, facilitating the appearance of the second hydration peak in the initial hydration period, and promote the hydration and hardening properties of blended cement. The adverse effects of alkali sulfates in clinker are alleviated with the addition of fly ash and slag; this can be attributed to the dilution and filler effects of supplementary cementitious materials (SCMs), as well as the effect of the alkali sulfates activating fly ash and slag. Arcanite, thenardite and aphthitalite (K3NS4) provide a better activating effect on mortar with slag than fly ash mortar to increase compressive strength and reduce drying shrinkage when the content of alkali sulfates is less than 0.6% sodium oxide equivalent (Na2Oeq).