A convenient synthetic approach for the synthesis of α‐oxo‐acetamidines via copper‐catalyzed C(sp3)‐H amidination has been developed. This approach allows the direct amidination of three C(sp3)‐H bonds without cyclization.Methyl ketones and primary and secondary amines are tolerant and afford the corresponding products in moderate to good yields. Furthermore, this protocol is also applicable to the synthesis of unsymmetrical α‐oxo‐acetamidines via one‐pot, multicomponent reactions (MCRs).