This work was designed to investigate the influence of arsenic dosage, variety on the mechanical properties, hydration, and solidification from the perspective of Portland cement (PC) performance evolution. The results demonstrate that using PC could solidify the arsenic wastes effectively, with arsenic leaching concentrations consistently below 5 mg/L. Arsenic wastes retard cement hydration, leading to a slower rate of hydrates formation, disrupting the calcium silicate hydrate (C–S–H) stacking structure, and thus detrimental to strength development especially at early age. The adverse effect is highly dependent on the arsenic variety. The insoluble calcium arsenate exhibits the least impact, while the arsenates show the largest challenging to immobilization due to the instability of hydrates. Molecular dynamic simulation indicates that arsenic can be chemically immobilized with Ca2+, and be physically adsorbed onto the positively charged C–S–H by forming As‐O···Ca···Si‐O units, accompanied by a significant reduction in adsorption energy by 46.5%. The arsenic solidification behavior provides a basis for the resource utilization of arsenic wastes in cementitious materials.