The effect of phosphogypsum (PG) on the hydration and retardation mechanism of phosphogypsum-based excess-sulfate slag cement (PESC) was mainly investigated. Based on the natural characteristics of PG, such as low pH value and the presence of soluble phosphorus impurities, the content of PG passing the 4.75 mm standard sieve was used as a variable to study the retardation mechanism of PG on PESC. It can be inferred from the heat flow and cumulative heat flow that the induction period is significantly prolonged with the content of PG, which is also reflected in the increase of the setting time of PESC. In the early period of hydration, as the content of PG increases, the soluble phosphorus concentration increases, and the pH value decreases. The changes in soluble phosphorus concentration and pH value affect the microstructure and amount of hydrates. Combined with experimental results, it has been demonstrated that the delay in the hydration of PESC by PG content is mainly due to: the excessive dissolution of Ca2+ and SO42- promotes the recrystallization of dihydrate gypsum; the dissolution of soluble phosphorus reduces the pH value in the pore solution and forms precipitates of calcium phosphate and hydroxyapatite; in the initial reaction period, a large amount of ettringite and C-S-H gel precipitate to form a protective film; the decrease in pH value leads to a decrease in carbonization resistance, and CO2 in the air is more likely to attack the PESC paste, react with alkaline substances in PESC, or degrade hydrated C-S-H and ettringite. The above factors all lead to a decrease in exchangeable ions during the hydration, thereby prolonging the setting of PESC.