Lee et al. reported a series of highly active single-site mesoporous Pd/Al 2 O 3 catalysts for selective aerobic oxidation of allylic alcohols. [9] Grassi et al. described gold nanoparticles enclosed in a polymer matrix for oxidative esterification of cinnamyl alcohol with alkyl alcohols. [10] Lee and co-workers developed a zirconia-supported ruthenium catalyst for efficient aerobic oxidation of alcohols to aldehydes. [11] Li et al. found that metal/oxide supported catalysts, such as FeO/Pt(111) or Cu 2 O/ Ag(111) exhibit interfacial effects that significantly improve the efficacy in the selective oxidation of primary alcohols. [4] These nanoparticle-based catalysts, though effective in mediating selective oxidation reactions, have significant drawbacks of high cost, low selectivity, and rapid deactivation in harsh conditions. As such, the development of more practical and economical catalyst systems has been a major challenge in both industrial and academic areas.In 2011, Zhang and co-workers, for the first time, presented a comprehensive study and coined the concept of single-atom catalysis. [12] As a new frontier, single atom catalysts (SACs) have gained wide attention because of their great advantages of high atom efficiency and unique catalytic activity. [13][14][15][16][17][18][19][20] SACs possess distinctive chemical and physical properties and a unique coordination environment that is different from their nanoparticle counterparts. [21][22][23][24][25] Moreover, SACs have been found to be effective in bridging homogeneous and heterogeneous catalysis. [26][27][28][29] Selective aerobic oxidation of alcohols offers an attractive means to address challenges in the modern chemical industry, but the development of nonnoble metal catalysts with superior efficacy for this reaction remains a grand challenge. Here, this study reports on such a catalyst based on atomically defined undercoordinated copper atoms over nitrogen-doped carbon support as an efficient, durable, and scalable heterogeneous catalyst for selective aerobic oxidation of alcohols. This catalyst exhibits extremely high intrinsic catalytic activity (TOF of 7692 h −1 ) in the oxidation of cinnamyl alcohol to afford cinnamaldehyde, along with exceptional recyclability (at least eight cycles), scalability, and broad substrate scope. DFT calculations suggest that the high activity derives from the low oxidation state and the unique co ordination environment of the copper sites in the catalyst. These findings pave the way for the design of highly active and stable single atom catalysts to potentially address challenges in synthetic chemistry.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/smll.202106614.