As a high biologically toxic heavy metal ion, Cr(VI) will cause environmental pollution and endanger human health. Therefore, the development of fast, simple and visible detection methods for Cr(VI) is extremely important to control its harm. Toward this end, we report the establishment of a colorimetric sensing method for Cr(VI) based on single-atom nanozymes for enhanced detection performance. Firstly, we prepared SA-Fe/NG as peroxidase mimetic by anchoring Fe single-atom onto a single-layer of two-dimensional nitrogen-doped graphene. The SA-Fe/NG showed superiorly high oxidation catalytic activity due to its 100% atomic utilization and existing Fe-N-C structure. Furthermore, with 3,3′,5,5′-tetramethylbenzidine (TMB) as a colorimetric sensing probe, and 8-hydroxyquinoline (8-HQ) as an inhibitor for the oxidation of TMB, the detection of Cr(VI) was realized through specific interaction between Cr(VI) and 8-HQ, which led to the recovery of oxTMB in blue color. Our established method showed superior sensitivity with a detection limit of 3 nM and a linear range of 30 nM to 3 μM. It also exhibited high selectivity for a series of metal cations, and has been successfully applied to the detection of Cr(VI) in tap water and tuna samples.