Utilizing the existing natural gas grid presents a promising method for transporting hydrogen on a large scale. However, the effects of natural gas and its impurities on hydrogen-assisted cracking in pipeline steel have not been adequately studied. This study aims to investigate the fatigue performance of X80 pipeline steel in hydrogen-enriched natural gas (HENG) environments and in mixtures containing the impurity CO2. This is achieved through fatigue crack growth rate (FCGR) tests and density functional theory (DFT) calculations. The experimental results show that the FCGR in H2 is slightly faster than that in HENG, whereas it is slower than that in the N2/CO2/H2 mixtures. The enhanced FCGR by CO2 further increases with the increasing CO2 content. DFT computational results indicate that the adsorbed CO2 on the iron surface significantly accelerates the migration of H atoms from surface to subsurface. This promotes the entry of hydrogen into the steel.