A series of iron-encapsulated hierarchical ZSM-5 zeolites with nanosheet-assembled structure were designed and successfully fabricated, and their catalytic performance was investigated for the selective catalytic reduction of NOx with NH3 (NH3-SCR). Because of the synergy between the well-dispersed Fe active species and the Bronsted acidic framework of zeolites, the Fe-containing ZSM-5 catalyst displayed excellent catalytic performance, and density functional theory (DFT) calculation data indicated that capturing NH3 was the main factor that mediates the NH3-SCR process. In addition, the resultant zeolite catalysts exhibited a good resistance to SO2 and H2O, which was very competitive for practical application to reduce NOx emissions. Furthermore, in situ DRIFT measurements revealed that the generation of inactive nitrate species led to the decrease of zeolite activity in a high-temperature region.