Pressure vessel steels are used in the manufacture of tanks for the storage of gases, chemical materials and oil. To meet the increasing production demands, high-wire-energy welding is widely used in the manufacture of pressure vessel steels. This means that the weldability of pressure vessel steels needs to be improved. Therefore, in order to reveal the microalloying effect of Ca in pressure vessel steel, this study took a commonly used pressure vessel steel as the research object, and three groups of experimental steels with different Ca mass fractions were prepared using vacuum metallurgy, controlled rolling and controlled cooling. Welding heat simulation technology was used to simulate the welding heat of experimental steel and the welding heat-affected zone (HAZ) was investigated. The inclusions of the welding HAZ in the experimental steels were observed by using a metallographic microscope and scanning electron microscope (SEM). The mechanism of intragranular acicular ferrite (IAF) nucleation induced by the inclusions containing Ca elements in the welding HAZ of pressure vessel steels was also discussed. The research results show that the addition of Ca increased the number density of effective inclusions in the welding HAZ of the experimental steel up to 535.60 pieces/mm2. The addition of the Ca element was beneficial for producing more pinning inclusions in the experimental steel welding HAZ under the experimental conditions, and the inclusions were mainly elliptical oxide complex inclusions of Ca-Si with a size of about 2 μm. Meanwhile, Al2O3 and MnS were precipitated. After the addition of Ca elements, Mn-poor regions appeared around the inclusions containing Ca in the welding HAZ. IAF nucleation was mainly induced by the local compositional change mechanism and supplemented by the stress–strain energy mechanism and inert interface energy mechanism. This study provides a valuable reference for optimizing the welding process of pressure vessel steels and is of great importance for understanding the IAF nucleation mechanism of Ca-containing inclusions in the welding HAZ of pressure vessel steels.