Although atomically dispersed Fe-N species as electrocatalysts often exhibit high activity for oxygen reduction reaction (ORR), the rational design and facile fabrication of single-atom Fe-N species-based catalysts remains a great challenge because of their easy aggregation. Herein, a new precursor of host-guest Fe-TPP⊂rho-ZIF (Fe-TPP = tetraphenylporphyrin iron; rho-ZIF = zeolitic imidazolate framework with the rho topology) for the first time was elaborately designed and readily prepared by one-pot mechanochemical method, and then was pyrolyzed into Fe-N/C catalysts with no need of solution-based steps and post-ammonia/acid treatments, which greatly simplified the preparation procedures. Owing to the host-guest confinement at the molecular level, the encapsulated Fe centers within interior cavities of rho-ZIF host matrice can be effectively isolated during pyrolysis to afford atomically dispersed Fe-N4 moieties anchored on the carbon matrice. Such a well-elaborated precursor not only endows the final product with the single-atom characteristic, but also with high Fe loading (up to 3.8 wt%) and specific surface area. Benefitting from the outstanding compositional and structural advantages, the resultant Fe-N/C exhibits highly efficient ORR activity with E1/2 of 0.895 V in 0.1 M KOH, ~ 50 mV more positive than that of the commercial Pt/C, which is among the top-level ORR electrocatalysts to date. It has excellent stability and displays a negligible change after a 10000-cycle accelerated durability test. Moreover, rechargeable Zn-air batteries were also assembled to demonstrate the practical application of the as-obtained Fe-N/C as air cathode catalyst. Our work may provide an insight into the facile and large-scale production of high-performance and durable non-precious metal catalysts with atomic-level dispersion.