Abstract Single‐atom materials (SAMs) have garnered widespread attention due to their maximum utilization of active metal atoms for catalytic related applications. However, the facile preparation of oxide materials with high single‐atom loading is still challenging. Herein, derivation of highly tunable metal‐organic frameworks (MOFs) precursor is found to be a potential method for the preparation of single‐atom Sn‐doped ZnO materials for high‐performance chemiresistive sensing applications. Specifically, Sn/Zn‐MOF‐L precursor with interdigitated lamellar morphology is transferred from bimetallic Sn/Zn‐MOF‐B featuring tunable microstructure and morphology through solvent treatment. Utilizing the finely Sn‐doped MOF as precursor, single‐atom Sn‐doped ZnO featuring nanosheet morphology and porous structure is successfully constructed. The as‐prepared single‐atom doped oxides show superior acetone sensing performances, as sensor based on 8% Sn‐doped ZnO demonstrates an astonishing response value of 213 ( R a / R g ) toward 10 ppm acetone and low detection limit of 0.52 ppb. The high sensitivity of Sn‐doped ZnO is attributed to the nanosheet morphology with high specific surface area and the distribution of single‐atom Sn active sites, benefiting from the manipulation of MOF precursor. The method for the preparation of single‐atom loaded oxides and their considerable sensing performance offers a new perspective for the design and application of SAMs.