<p>Oximes are used in many scientific and industrial domains, ranging from organic synthesis through biotechnology to materials science. Traditionally, their synthesis necessitates the use of hydrocarbons with specific functional groups, such as carbonyls, which are often more challenging and expensive to obtain compared to their non-functionalized counterparts. Here we introduce an approach that enables the synthesis of oximes from hydrocarbons via the oxidative oximation of methylene C-H bonds — the most prevalent molecular unit in the world of molecules. Under the catalysis of a manganese complex with hydrogen peroxide as the oxidant and hydroxylamine sulfate as the amine source, we demonstrate that a diverse array of molecules — from simple chemicals like propane and cyclohexane to complex compounds such as the antimalarial drug artemisinin — can be oximated at methylene C-H bonds with synthetically significant yields under mild conditions. The catalyst displays a good level of functionality tolerance and often predictable site selectivity in complex molecule settings. Our approach opens an avenue for oxime synthesis and is anticipated to have broad applications in the production of fine and commodity chemicals, bioactive molecules, and new materials.</p>