This study examined the effects of alloying elements (C, Mo) on hydrogen-induced cracking (HIC) and sulfide stress cracking (SSC) behaviors of A516-65 grade pressure vessel steel in sour environments. A range of experimental and analytical methods of HIC, SSC, electrochemical permeation, and immersion experiments were used. The steel with a higher C content had a larger fraction of banded pearlite, which acted as a reversible trap for hydrogen, and slower diffusion kinetics of hydrogen was obtained. In addition, a higher hardness in the mid-thickness regions of the steel, due to center segregation, resulted in easier HIC propagation. On the other hand, the steel with a higher Mo content showed more dispersed banded pearlite and a larger amount of irreversibly trapped hydrogen. Nevertheless, the addition of Mo to the steel can deteriorate the surface properties through localized pitting and the local detachment of corrosion products with uneven interfaces, increasing the vulnerability to SSC. The mechanistic reasons for the results are discussed, and a desirable alloy design for ensuring an enhanced resistance to hydrogen assisted cracking (HAC) is proposed.