The present research estimates fatigue life of a type-IV CNG composite cylinder of a road automobile that serves as a super-acute part from a safety perspective. This component is subjected to cyclic internal pressure due to filling and emptying the cylinder. To this end, the mechanical and fatigue properties of different materials were determined experimentally. Transient dynamic analysis was performed to obtain the stress tensor as a function of time in the critical zone using Finite Element (FE) simulation. Next, fatigue life of this critical component was assessed utilizing 3D stress components and employing some well-known fatigue failure criteria for composite materials. The FE and tests results were compared. The most important achievement of the research is that the Epaarachchi and Clausen, Fawaz–Ellyin, and Harris and Gathercole criteria ensure the highest precision (15, 17, and 18% error) for fatigue life assessment of this critical component.